TW201020257A - Spiro-oxindole compounds and their use as therapeutic agents - Google Patents

Abstract

This invention is directed to spiro-oxindole compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

Description

201020257 VI. Description of the Invention: [Technical Field] The present invention relates to a spiro (9) anthrone compound, a medicine comprising the compound, and a β substance, and the use of the compound and a pharmaceutical composition for treating a sodium channel-mediated disease Or symptoms (such as pain) and other methods associated with the media and channels of sodium channels. [Prior Art] The electrical φ Μ pass-through channel transmembrane protein that triggers the action potential in nerves, muscles, and other electro-active cells is necessary for normal perception, emotion, thinking, and movement (Catterall, WA·, iVaiwre (2001), Vol. 4, 9, pp. 988_990). These channels contain highly processed "subunits, which are related to the auxiliary subunits. The subunits that form the pores are sufficient for channel function, but the dynamics and voltage dependence of the channel gating are one The copies were modified by the Wanya unit (Goldin et al., 汾 伽 (2000), vol. 28, pp. 365-368). Each <2-subunit contains four synonymous functional sites j to IV, each with six The predicted transmembrane segment, which forms ion-conducting pores and contains a sodium channel a_ subunit that regulates sodium ion conduction, with a relative molecular mass of 260,000. Electrophysiological recording, biochemical purification, and molecular Asexual reproduction, ten different sodium channel a subunits and four million subunits have been identified (%, RH. et al., (2004), 253; with YU, FH, etc., squad (2_, 20: 7577-85) The positive subscript of the nanochannel includes the fact that when the voltage across the stimulating cell plasma membrane is depolarized (voltage dependent strobe), and the sodium ion is effectively and selectively conducted through the conductive pores inherent to the protein structure Rapid activation and inactivation (Sat〇, c 143924-sp -20091127-1 201020257 et al, Mm/re (2001), 409: 1047-1051). At negative or excessively polarized membrane potential, the sodium channel is shut down. After depolarization of the cell membrane, the sodium channel will rapidly The ground is turned on and then inactivated. The channel conducts current only in the on state, and once deactivated, it must return to the quiescent state before it can be reopened, which is facilitated by cell membrane hyperpolarization. Different sodium channel subtypes are The voltage range under activation and inactivation and its activation and inactivation mechanics have changed. The sodium channel population of proteins has been extensively studied and has been shown to be involved in a variety of life functions. Studies in this field have confirmed CK subunits. A variant that causes a major change in the function and activity of the channel, which can ultimately lead to pathophysiological symptoms. As a function of the implicature, this proteome is considered a driving point for therapeutic intervention. Nav 1.1 and The Nav 1.2 line is highly expressed in the brain (Raymond, CK et al., X β illusion. CTiem. (2004), 279(44): 46234-41)' and is important for normal brain function. Medium, in Nav 1.1 Mutations in Nav 1.2 can cause severe epileptic states, and in some cases, mental decline (Rhodes, TH et al., /Voc·iVai/. Actzci. >Sd·USA (2004), 101(30): 11147-52; Kamiya, K. et al., /· C/im. (2004), 24(11): 2690-8; Ο

Pereira, S. et al., Magic; (2004), 63(1): 191-2). Therefore, the two channels w have been considered to be validated targets for the treatment of epilepsy (see PCT Publication No. WO 01/38564).

The Nav 1.3 system is widely expressed throughout the body (Raymond, C.K. et al., in the literacy of 2 歹/遂). It has been shown that in the dorsal horn sensory neurons of rats after neurological injury, it has its upward regulation (Hains, BD et al., / iVewrasd. (2003), 23(26): 8881-92). . Many experts in this field have identified Nav 1.3 as an appropriate target for pain therapeutics (Lai, J. et al., Cmh: (9/^· 143924-sp-20091127-l (S) 201020257 (2003), ( 3): 291-72003; Wood, JN, et al, X (2004), 61(1): 55-71; Chung, JM, et al, A^vartk Fowm/ Office/?. (2004), 261: 19 -27; Discussion 27-31, 47-54) 〇

The performance of Nav 1.4 is basically limited by muscle (Raymond, C.K. et al., the author of the above article). Mutations in this gene have been shown to have profound effects on muscle function, including pruritus (Tamaoka Α., /«iem. Mec/. (2003), (9): 769-70). Therefore, this channel can be considered as a marker for the treatment of abnormal muscle contraction, spasms or itching. The Spring Heart Na channel Nav 1.5 system is mainly expressed in the ventricles and atrium (Raymond, CK· et al., on the X歹/遂之遂), and can be found in the sinus node, the chamber section and possibly the Pu In gold Ehrlich cells. The rapid overshoot of the cardiac action potential and rapid pulse conduction through the heart tissue are due to the opening of Nav 1.5. Therefore, the Nav 1.5 system is the origin of the heart rhythm. Mutations in human Nav 1.5 cause multiple rhythmic syndromes including, for example, long QT3 (LQT3), Brngada syndrome (BS), genetic heart conduction defects, sudden accidental nighttime death syndrome (SUNDS), and sudden infant death Syndrome (SIDS) (Liu, w Η. et al., Am. /. (2003), 3(3): 173-9). Nanochannel blocker therapy has been widely used to treat cardiac rhythm. The first anti-arrhythmic drug, quinidine, discovered in 1914, was classified as a sodium channel blocker.

The Nav 1.6 system enables a large number of widely distributed voltage-gated sodium channel codes that are found throughout the middle and peripheral nervous systems, clustered in the Ranvier section of the axon (Caldwell, JH et al., iVoc. iVaiZ. Acad Sd. USA (2000), 97(10): 5616-20). Although no mutants have been detected in humans, the Nav 1.6 line is recognized as 143924-sp-20091127-1 201020257 as a role in the appearance of symptoms associated with multiple sclerosis and has been considered to treat this disease. Subject (Craner, MJ. et al., corp. rac. iVai/. Aawl Sd. USA (2004), 101(21): 8168-73).

The Nav1.7 line was first asexually propagated from the pro-chromoblastoma PC12 cell line (Toledo-Aral, J. J. et al., corpus wc. Μζ". Ααζί/. Sd. USA (1997), 94: 1527-1532) . It is present in high growth cells in growth cone cells of small diameter neurons, indicating that it can play a role in the transmission of nociceptive messages. However, this has been challenged by experts in this field, as Nav 1.7 is also expressed in neuroendocrine cells associated with the autonomic system (Klugbauer, N. et al., J. (1995), 14(6): 1084-90), and It has already implicated the autonomous process itself. The implied role in autonomic function was confirmed by the absence of Nav 1.7 mutants; deletion of Nav 1.7 in all sensory and sympathetic neurons resulted in phenotypes before and after death (Nassar et al., corpus wc. he" Acad USA (2004), 101(34): 12706-11). In contrast, in a subset of sensory neurons that are primarily nociceptive, a role in the pain mechanism is confirmed by deleting Nav 1·7 expression (Nassar et al., in J: Wen Zhizhi) Luxury #户). Further support for the activity of Nav 1.7 blockers in a subset of neurons is supported by the following findings: two human hereditary pain symptoms, primary acral red pain and familial rectal pain, have been confirmed The map was formed to Nav 1.7 (Yang, Y. et al., Weng. Genei. (2004), 41(3): 171-call).

The performance of Nav 1.8 is basically limited to DRG (Raymond, C.K. et al., J: wenzhizhi #家). There are no confirmed human mutants for Nav 1.8. However, mutant mice without Nav 1.8 survive, fertile and normal appearance. Significant pain relief for noxious mechanical stimuli's lack of harmful heat perception 143924-SP-20091127-1 -6- 201020257 Loss, and delayed development of inflammatory hyperalgesia, the researchers pointed out that Nav 18 in the pain message The Department plays a major role (Akopian, A N. et al., Chest (10), Jan. (1999), 2 (6): 541-8). The blockade of this channel is widely accepted as a potential treatment for pain (Lai, J et al., by the side of the ## Yin; Wood, JN et al., the work of the above-mentioned work; household; Chung, j M Waiting for someone in J: and then swearing #尹). The PCT published patent application, w〇〇3/〇37274A2, describes the p-pyro-pyrugamine and the scented amines used to treat central or peripheral nervous system symptoms, particularly pain and chronic pain, by blocking Sodium channel beta associated with the development or recurrence of the indicated symptoms. Patent Application WO 03/037890 Α 2 describes the hexahydropyrazole class to treat central or peripheral neuropathic symptoms, particularly pain and chronic pain, in a manner It is a block of sodium channels that are associated with the onset or recurrence of the symptoms shown. The compounds, compositions and methods of the invention are particularly useful for the treatment of neuropathogenic or inflammatory pain by inhibiting the passage of ion flux through a channel comprising a ΡΝ3 (Nav 1.8) subunit. Tetrodotoxin-insensitive terminal sodium channel Nav 1.9 as revealed by Dib-Hajj, SD et al. (see Dib-Hajj, SD et al., Ptoc. MziZ. Acad Sd. USA (1998), 95(15): 8963- 8) It has been confirmed that it is only resident in the dorsal root ganglion. The Nav 1.9 line has been shown to be the basis for the depolarization and excitability caused by neurotrophins (BDNF) and is the only member of the sodium channel supergroup that has been shown to be mediated by the voltage of the ligand (Blum, R., Kafitz). , KW, Konnerth, A., TVaiwre (2002), 419 (6908): 687-93). The limited type of performance of this channel has made it a candidate for the treatment of pain (Lai, J et al., in the case of i Wenyu, Yin; Wood, JN, et al., in the book of the text; Chung, JM, etc. , in 143924-sp-20091127-1 201020257 cited in the above works.

NaX is the inferred nanochannel, and the heading is unverified as a voltage gating. Except in the lungs, heart, and dorsal hernia; A々 month W is very close to the nerve and peripheral nervous system

In Schwann cells, NaY p has been found in neurons and ependymal cells in the restricted regions of the CNS, especially in the periventricular organs. Body fluid stability (Watanabe Ε笪ar Ar c, 匕寺人, 乂iVe Qingyang·(2〇〇〇), 2〇(2〇): 7743-5D. No thief mouse in water _ with salt depletion Under the conditions, it shows that the sputum is infiltrated with osmotic saline. These findings indicate that the regulation of the central sensation of the body fluid and the salt uptake behavior of the body fluid plays an important role. Its performance and function suggest it as a treatment for gallbladder fibers. Degeneration and other related salts regulate the symptoms of the disease. 'The study used to reduce brain. The sodium channel blocker of neuronal activity in some areas of dioxin OTX.' shows its potential use in addiction treatment. Stimulation of drug pairing will induce t-sex and domain recurrence and drug-seeking behavior in rats. The functional integrity of the base and lateral tonsils (BLA) is the result of the stimulation induced by the coca test. It is necessary to recover from the search for behavior, but not by Ke Qi itself. BLA plays a similar role in the recovery of heroin search behavior. BLA has been adjusted for the heroin search behavior in the rat model and the TTX-recovery of the sea (4) priming recovery (uchs, RA ^ See, RE, Psychopharmacology (2002) 160(4): 425-33) "The relevant protein group has been identified as a therapeutic intervention since it has been identified, and the nanochannel system has been labeled with various arrays of pharmacological agents. It includes neurotoxins, anti-turning drugs, anticonvulsants and local anesthetics (ckre, 143924-sp-2〇〇9ll27-l 201020257 Liao et al., 琬/七痹##现(2000) 5: 506-520 ). All current pharmacological agents acting on the sodium channel have receptor positions in the alpha subunit. At least six different carcass locations for neurotoxin use, and a local anesthetic and related drug for a receptor site have been identified (Ce herle, S. et al., vol. 82, pp. 883-892). Small molecule sodium channel blockers or local anesthetics and related anti-epileptic drugs and anti-arrhythmic drugs interact with overlapping receptor sites located in the pores of the sodium channel pores (Catterall, WA, 旎清„ (2000), 26 : 13_25). The amino acid residues in the S6 segment derived from at least three of the four functional sites contribute to the location of the complex drug receptor, with the IVS6 segment playing a dominant role. Equal regions are highly conserved, and thus most of the sodium channel blockers known to date interact with all channel subtypes with similar efficacy. However, they have been able to produce sodium with therapeutic selectivity and adequate therapeutic window Channel blockers for the treatment of epilepsy (eg lam〇trignine, phenytoin and methotrexate) and certain cardiac rhythm disorders (eg lidocaine, tocainide) And mexiletine. However, the efficacy and therapeutic index of such blockers are not optimal and have limited the effectiveness of such compounds in a variety of therapeutic areas where the sodium channel blocker is ideally suited. Sexual and Chronic Pain Treatment Therapy is the only reliance on acute and chronic pain in all age groups, including newborns, infants and children. Pain medications are classified into three main categories by the American Pain Society: Opioid analgesics acetaminophen and non-steroidal anti-inflammatory drugs, including salicylate (example 143924-sp-20091127-1 201020257 such as aspirin), 2) opioid analgesics, and 3) Analgesics. Non-opioid analgesics, such as acetaminophen, and NSAIDs, can be used for acute and chronic pain, including surgery, trauma, arthritis, and cancer, for a variety of reasons. NSAIDs are needed for pain involving inflammation, Because acetaminophen lacks anti-inflammatory activity, opioids also lack anti-inflammatory activity. All nsaid inhibit cyclooxygenase (COX), thus inhibiting prostaglandin synthesis and reducing twin pain response. There are at least two COX isomeric recombinations. , l and COX-2. Commonly used non-selective cox inhibitors include ibuprofen (ibupr〇fen) and naproxen. COX-i is found in platelets, 〇1 In the kidneys and most other human tissues, the inhibitory line is thought to be associated with adverse effects such as gastrointestinal bleeding. Selective c〇x_2 NSAID development, such as Celecoxib, Videkusibi (Valdec〇xib) and Rofecosi (*coxib) have the benefit of non-selective NSAIDs, with a reduction in adverse effects in the intestines and kidneys. However, current evidence suggests that chronic use of certain selective inhibitors may It can increase the risk of stroke. The use of steroidal opioid analgesics is recommended by the American Society (IV), based on the medical history of pain and the body including repeated pain assessment. From: With the broad and unfavorable form of opiate use, therapy should be included in the treatment: integration of interdisciplinary treatment plans and appropriate current patient monitoring. Advance: Negative opioids should be added to non-opioid opioids to deal with acute pain and cancer-related pain that would respond to early non-growth. An opioid analgesic agent, in the pivotal and peripheral nervous system, acts as a stimulant. You can touch „ ^ ^ ^ ^ 片片 and its formula or mode of administration, which can have a long duration. All opioid analgesics can cause 哞143924-sp-20091127-1 -10- 201020257 to inhibit, The risk of liver failure, palpation and dependence, and its own treatment for chronic pain or pain is not ideal. ^ This can enhance the role of opioids, have an independent analgesic activity in a certain 18 or neutralize the side effects of analgesics The role of non-official music is generally referred to as "common painkiller". Bicyclic antidepressants, antiepileptic drugs, local anesthetics, corticoid bone muscle relaxants, anticonvulsants, antihistamines, benzodiazepines, caffeine, topical agents (eg Capsaicin), dextroamphetamine and well H

The classes are all used clinically as M% adjuvant therapy or individually for the treatment of pain. In particular, anti-epileptic drugs have enjoyed some degree of success in treating pain symptoms. For example, Gabapentin, which has an unconfirmed treatment = is required for neuropathic pain. Other clinical trials are attempting to establish a central neuropathic pain that responds to ion channel blockers, blockers such as mom, sodium, and/or green methyl D-aspartate. Currently in development are low-affinity NMDA channel blockers for the treatment of neuropathic pain. The literature provides pre-injection electrophysiology that supports the use of NMDA antagonists to treat neuropathic pain. This agent has also been found to control pain after the occurrence of resistance to opioid analgesia, especially in cancer patients. The systemic analgesic agent, such as sputum and opioids, is intended to be distinguished from a therapeutic agent that can only be used as a local analgesic/anesthetic. Conventional topical analgesics, such as lidocaine and serocaine, are non-selective ion channel blockers, which can be fatal when administered in a systemic manner. A description of non-selective sodium channel blockers can be found in Madge, D. et al., 乂 from C/iem. (2001),: 143924-sp-20091127-1 201020257 115-37. Several sodium channel modulators are known to be useful as anticonvulsants or antidepressants, such as carbamide, amitriptyline, lamotngine, and riluzole, All were based on the brain tetrodotoxin-sensitive (TTX-S) sodium channel. Such TTX_s agents suffer from limited dose side effects, including dizziness, dysregulation, and drowsiness, primarily due to the effects of TTXs in the brain. The role of the sodium channel in pain in sodium plays a role in maintaining a normal and pathological state, including the voltage-gated sodium channel in abnormal neuronal activity and neuropathogenic or pathological pain. Played a long-established role (Chimg' JM· et al., in the context of 2 essays. The damage to peripheral nerves after trauma or disease may cause abnormal activity of sodium channel activity and development. Alterations include ectopic emissions from axonal resection of afferent and sensitized intact nociceptives. These changes can result in long persistent allergic or abnormal sensations of normal innocuous stimuli. Examples of neuropathic pain Including but not limited to post-herpetic neuralgia, tri- and neuralgia, neuropathy in patients with glucosuria, chronic lower back pain, fantasy limb pain and pain caused by cancer and chemotherapy, chronic pelvic pain, complex regional pain syndrome And related neuralgia. On the treatment of neuropathic pain signs, there is some kind of Chengchengli using drug therapy such as gabapentin (gabapenti) n), and the most recent Pregabalin (P g ) # is the New Zealand first-line treatment drug. However, %, for the neuropathic I. Pain medicine therapy, in general, has limited success, right Commonly used 143924-SP-20091127-1 (S) -12. 201020257 Pain-lowering drugs, such as NSAIDs and opiates, "have no response. Therefore, there is still considerable demand for the discovery of new treatment forms. The most potential effective sodium channel Blockers are clinically associated with non-spray J events. There are also unmet medical needs to treat neuropathic pain and other sub-channel related states effectively and without == use. The present invention provides this. SUMMARY OF THE INVENTION The present invention is directed to a spiro compound, and a pharmaceutical composition comprising the same, and the use of the compound of the present invention and a pharmaceutical composition for treating and/or preventing a disease or symptom of a subchannel (# Method of treating pain, etc. The present invention is also directed to a method of treating a disease or a silk that is mediated by other compounds of the present invention using a compound of the present invention and a medicinal composition comprising the compound of the present invention. But not limited to central nervous symptoms, such as epilepsy, anxiety, depression = bipolar disease; cardiovascular symptoms such as arrhythmia, atrial fibrosis: and ventricular fibrillation; neuromuscular symptoms, such as restless foot syndrome, spontaneous tremor And muscle paralysis or tetanus; resistance to wind nerve compliance, glaucoma, nerve damage and multiple sclerosis; and channel diseases, such as acral red pain and familial rectal pain symptoms. The present invention is also directed to the compounds of the present invention The use of a pharmaceutical composition comprising a compound of the invention for the treatment and/or prophylaxis of a disease or condition such as hypercholesterolemia, benign prostatic hyperplasia, scrapie and cancer. Thus, in the aspect of the invention, the invention is directed to 1) Compound: 143924-sp-2009l 127-1

13 201020257

Wherein: η is 1 or 2; one of J and Κ is _Ch2-, and the other is or both J and K are -CH2-; R1 is gas, sulfhydryl, cyclopropyl, fluorenyl, ( 3-carboxyl group, (3_sulfonylamino) yl, [(3-methylsulfonylamino)pyridin-2-yl]methyl, [(3_carboxy> than bite- 2-yl]fluorenyl, [(ethoxy)-reactive] fluorenyl, 2-cyclopropylethyl, 1,3-oxazol-5-ylindenyl, 3-methoxypropyl, (6 -mercaptopyridine-2-yl)methyl, acridin-3-ylindenyl' [3-(cyano)-pyridyl-2-yl]indolyl, [3-(difluoroindolyl) 2-yl]fluorenyl, 3-(5-methyl-1,2,4-oxadiazol-3-yl)-yl, 4-(5-fluorenyl-1,2,4)diazole- 3-yl) benzyl, [5-(trifluoromethyl)-!, 2,4-oxadiazole-3-yl] fluorenyl, [5-(trifluoromethyl)-1,3,4 No. 2-2-yl] fluorenyl, [4-(tri-I fluorenyl) guan-2-yl] fluorenyl, (4-methyl-i, 2, 5 j dis-3-yl) Methyl, oxime -2-methylmethyl, pyrimidine-2-ylmethyl, (i-methyl-1H_benzotriazole·5_yl) ❹ methyl' [2-(third-butyl) Oxysterylamino)P is more than _5_yl]methyl, [6_(dioxamic V is more than -3-yl)methyl, [6-(di) Base>biter-2-yl]methyl, (6_[(-)-methylene)amino]17 than sigma-2-yl}methyl, (5-?!!) 林_4_基P-pyridin-2-yl)methyl'[5-(dimethylaminoacridin-2-yl)methyl, (6-aminopyridin-2-yl)methyl, (6-yl-1) , 6-dihydro ρ than -3-yl) fluorenyl, (2-thiopyro-5-yl)methyl, (1-methyl-6-keto-1,6-dihydropyran ratio咬-3-yl) fluorenyl, (6-amino p to -3-yl)methyl, [1,2,4] three "sit and [l,5-a]p than bite-6-yl Methyl, 143924-sp-20091127-1 -14- 201020257 (5-hydroxypyridin-2-yl)methyl, (5-bromopyridin-2-yl)methyl, decylcarbonylmethyl, [6- Deoxy-D-semi-milk called 〇南糖], (6-?-fu-P--4-yl I»pyridin-3-yl)methyl, [3-(methylsulfonyl)p-pyridin-2 -yl]fluorenyl, (4S)-2,2-dimethyl-1,3-dioxoindol-4-yl]methyl, (3-bromopyridin-2-yl)methyl, [( 2-醯iminocarbamimidyl)pyridin-5-yl]methyl, (6-cyanopyridin-2-yl)methyl, (6-aminocarbonylpyridin-2-yl)methyl, two Benzyl, 4-methoxy-aryl, 2-(fluoromethyl)-yl, 2-ethoxyethyl, 4 -fluorophenyl, (2-fluorophenylaminocarbonyl)methyl, 2-(2-methoxyethoxy)ethyl, 4-isoxazole-5-ylbenzyl, 3-(benzyloxy) Propyl, (2S)-2,3-dihydroxypropyl, 4-methoxybutyl, pentyl, isopentyl, hexyl, 3-nitrobenzyl, [3-(trifluoromethyl) >Bipyridin-2-yl]methyl, [5-(trifluoromethyl)acridin-2-yl]methyl, [(t-butoxycarbonylamino)acridin-2-yl]- , (3-(trifluoromethyl oxaridin-2-yl) fluorenyl, (5-(trifluoromethyl)furan-2-yl) fluorenyl, tetrahydrofuran-2-yl fluorenyl, 3-fluorenyl Butyl, cyanoguanidino, 4-hydroxybenzyl, 3-cyanobenzyl, 4-fluoro-3-methoxybenzyl, 4-cyanobenzyl, [6-(trifluoromethyl) Acridine _3_yl] fluorenyl, [4-(trifluoromethyl carbazole-2-yl) fluorenyl, (3-fluoropyridin-2-yl) fluorenyl, (4-based I? ratio Bite _2_yl)methyl, (5-1 py p to _3_yl) methyl, (5-fluoropyridin-2-yl) fluorenyl, (3-chloropyridyl-2-) Base, sulfhydryl, (3,5-difluoroindan-2-yl)methyl, (3_acridine_3_ylisoxazole-5-yl)methyl, (2,2-difluorocyclo Propyl)methyl, 2-ketobutyl, 2,1,3-benzene Pyrimidazole-5-ylmethyl, 2,1,3-benzoxadiazole-5-ylindenyl, 1,3-benzoxazol-2-ylmethyl, (1_methyl·1Η_benzene And imidazol-2-yl)indolyl, [2-(1-mercaptoethyl)-n, pyrazol-4-yl]fluorenyl, tert-butoxycarbonyl, [1-(third-butoxy) Carbonyl)hexahydropyridin-4-yl]methyl, (2-methoxypyrimidin-5-yl)methyl, (6methoxypyridine each 143924-sp-20091127-1 -15- 201020257 base) methyl , (1-Iso-pyridin-2-yl)methyl, (3-aminopyridin-2-yl)methyl, hexahydroacridinylmethyl, [1-(1-mercaptoethyl)hexahydropyridine 4-yl]methyl, (1-methylhexahydropyridin-4-yl)indolyl, phenanthroline-2-ylindenyl'[4_(1_decylethyl)norfosyl-2-yl ]methyl, (4-mercapto-whufolin-2-yl)methyl, (2S)-norfos-2-ylindolyl, [(2S)-4-indolyl-norfosyl-2-yl ] mercapto, [5-(-I-indolyl)pyran-2-yl]indenyl, tetrahydro-2H-bran-4-ylmethyl, tetrahydro-2H-pyran-2-ylmethyl , (5-alkyl-1·methyl-1H-imidazol-2-yl)methyl, (6-aphthyridin-2-yl)methyl, (4,6-dimethoxypyrimidine_2_ Methyl, [(3-nonylaminocarbonyl) Oxaridin-2-yl]methyl, 1-[2-(aminoethyl)aminocarbonylcarbonyl-3-pyridin-3-yl]decyl, pyridin-2-ylindenyl, _2_ylmercapto, 1,4-dioxoin-2-ylindenyl 3,4-dimethoxyoxy, 3,5-dimethoxybenzyl, 3-hydroxypropyl, 3-o-phthalimidopropyl, 3-aminoindenyl, (3-aminomethyl)hanyl, (4-aminomethyl)-, (3_N,N-dimethylamino) Carbonyl)hanyl, 4-(benzyloxy)benzo, 4-fluorobenzyl, 2,3-difluorohanyl, 3,5-difluoroindolyl, 2-carbyl-4-fluorobenzyl, P-(2-Fluorophenyl)aminocarbonyl]ykyl, 3-(methoxycarbonyl)hanyl, 4-(indolylcarbonyl)aryl, 4-(ethyllactosyl)-yl, 3-( Dimethylamino-continuation base) Hanji, 3_(3_mercapto®-l, 2,4-p II. Sitting on a 5-base), 4-(3-amino-lH-p than spani-5-yl), 4-(3-methyl-1,2, deuterated-5-yl) Word group, 3-(isfosyl fluorinyl) group, 2-(difluoromethyl)-yl, (3-trifluoromethoxy)-, (2-fluoro-trifluoro) Base, fluorenyl, (2-fluoro-5-trifluoromethyl)decyl, (2-trifluoromethoxy)benzyl, 3-(amino(imido)methyl)-yl] 2_Amino 2-(hydroxyimino)ethyl, (6-(Ν'_)-based hydrazide-ylamino) ρ than bityl 3-methyl), 2-(2,2 '5-Dimethyl-1,3-dioxoindole-2-yl)ethyl, (4-fluorenyl ruthenium 225- 143924-sp-20091127-1 -16· 201020257 base) methyl, [(2S)-4-benzylfosfolin-2-yl]methyl, 2,3-dihydro-1,4-benzodioxanthene-6-ylmethyl, [5-(three Fluoromethyl)furan-2-yl]methyl, 3-(trifluoromethyl)benzyl, [3-(trifluoromethyl)pyrene-2-yl]methyl, [4-(trifluoro)曱基风乙-3-yl]methyl, (5-methoxybenzyl-2-yl)methyl, 5-carboxyfuran-2-ylmethyl, 5-(dioxylcarbonyl)furan -2 benzyl, [2-(trifluoromethyl) aridin-3-yl] fluorenyl Methylcarbonyl, ethoxycarbonyl, tert-butoxycarbonyl or [(3311, 511, 535, such as 5 to 11)-2,2,7,7-tetramethyltetrahydro-3 sister-double [U] II Oxazepine[4,5-b : 4',5'-d]piperidin-5-yl]indolyl; ❹ each R 2 is independently hydrogen, hydroxy, amine, (hexylaminocarbonyl) Amino, (cyclopentylaminocarbonyl)amine, arylamino, (cyclohexylaminocarbonyl)amine, methanesulfonylamino, (methyl)carbonylamino, N,N-dimethyl Aminocarbonyl, (ethyl)carbonylamino, (butyl)carbonylamino, (tri-butyl)carbonylamino, (pentyl)carbonylamino, (hexyl)carbonylamino, ( Methoxymethyl)carbonylamino, cyclobutylcarbonylamino, [2-methoxy(ethoxyindenyl)]carbonylamino, (sulfonyl)amino, (2-trifluorofluorene) Alkylamino), (cyclohexyl)carbonylamino, (cyclopentyl)alkylamino, (cyclopropyl)carbonylamino,

A zero (phenyl)carbonylamino, bromo, cyano, fluoro, decyl, decyloxy, hydroxycarbonyl, methylcarbonyl, tetrahydropyrrolylcarbonyl, aminocarbonyl, anthranylcarbonyl, (2 -nonyloxyethyl)aminocarbonyl, (cyclopropyl)aminocarbonyl, pentylaminocarbonyl, (cyclobutyl)aminocarbonyl, (cyclopentyl)aminocarbonyl, hexylaminocarbonyl , (cyclohexyl)aminocarbonyl, (4-fluorophenyl)aminocarbonyl, (4-fluorobenzyl)aminocarbonyl, indole-2-ylmethyl)aminocarbonyl, 2-(2- Ethoxyethoxy)ethoxy, [3-(trifluoromethyl)>pyridin-2-yl]oxy, quinolyl, phenoxycarbonyl, 2-ketononenyl, 2- Ketotetrahydropyrrolyl, 143924-sp-20091127-1 -17· 201020257 morpholinyl, 2-ketopyridyl, benzyloxy, [3_(trifluoromethyl) 峨_2_ yl] oxime Base, biting-2-yloxy, pyridin-2-yloxy, 4 (trioxinyl)phenoxy, 2-mercapto-1,3-pyrazol-4-yl, 2-amine Base_ι,3_thiazole ice-based, 6-(dioxin-amino-piperidin-3-yl, furanyl, 1H-p-pyrazole-3-yl, 1H-pyrazol-4-yl, 1-methyl-1H -pyrazol-4-yl, 5- Benzyl-1H-pyrazole-3-yl, 5-mercapto-1,2,4-dioxa-3-yl, (6-decyloxy-3-yl)oxy, 13-benzoic Oxyxene-5-yloxy, 4-fluorodecyloxy, 3,5-dimercaptoisoxazole-4-yl, phenoxy, 3-methoxyphenoxy, 4 oxime Phenoxy, 3-morpholine-4-ylphenoxy, 4-fluorophenoxy, 4-decyloxyphenyl or 4-phenylphenylphenyl; or two adjacent R2 and their The attached adjacent carbons together form a fused pyrimidine ring, a fused p-bite ring or a fused dioxinyl ring; for its stereoisomers, palm toomers Or a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention is directed to a compound:

Wherein: each R3a is hydrogen or a fluorine group; R3 is hydrogen, methyl, 3-, methyl, 3-(trifluoromethyl)pyridyl-2-yl]methyl, 2,5-dimethyl Small (1_methylethyl)-1Η-pyrrol-3-yl]methyl, (3-isopropylisoxazole-5-yl)methyl, (4-mentyl-2-thienyl)methyl , 1-benzofuran-2-ylmethyl, [2- 143924-SP-20091127-1 -18- 201020257 methyl-5-(trifluoromethyl)-l,3-oxazol-4-yl] Methyl, [5-(4-phenylphenyl)-2-(trifluoromethyl)furan-3-yl]methyl, [5-chloro-1-methyl-3-(trifluoromethyl) -iH-pyrazol-4-yl]methyl, 5-methoxypyridin-3-yl, 4-bromodecyl, [(2S)-5-ketotetrahydropyrrol-2-yl]methyl , cyanomethyl, [5-(trifluoromethyl-3-fluoromethyl)methyl, (5-chloro-2-nonyl)methyl, (3-chloropyrimen-2-yl)methyl , [3-(2,6-di-phenylphenyl)-5-fluorenyliso-4-yl]methyl, {2-[4-(trifluoromethyl)phenyl H,3-indole Zin-4-yl}methyl, (5-phenyl-l,3,4-oxadiazol-2-yl)methyl, [5-(4-chlorophenyl)-1,3,4-indole Di-indol-2-yl]methyl, [1,3]oxazolo[4,5-b]pyridin-2-ylindenyl, (2-isopropyl-1,3-p-stazole-5-yl) ) Mercapto, (2-isopropyl-1,3, oxazol-5-yl)methyl, 3-(tris-butoxycarbonylamino)·3_(cyclopropyl)propyl, 4-(曱Thio)benzyl, 2-cyanoethyl, (2-bromo-indole, 3-hydrazin-5-yl)methyl, [2-amino-4-(trifluoromethyl)-1, 3_thiazole_5-yl]indenyl, (2-amino-1,3-ρ-[oxazol-4-yl)methyl, (5-chlorothiophen-2-yl)indolyl, decylethyl )-1,3-pyrazol-4-yl]fluorenyl, (5-a gas-based, 2,4-pyrazol-3-yl) fluorenyl, (5-alkyl-1,2,4 -ρ塞二"Sit-3-yl)methyl, 4-decyloxyindenyl, (2S)-1,4-dioxoindolin-2-ylindenyl, (2-carbyl-ι, 3 _ 嘧 _ 5 5 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 -p-supplemental -5-yl)methyl, (2-hexahydrop-biti-1-yl-l, 3-indolyl _5-yl)methyl, (2_decyloxy-1, 3-portoindole-5-yl)methyl, 2-[5-(trifluoromethyl).up No. 2 _3_yl] ethyl, [5-(trifluoromethyl)-1, 2,4-oxadiazole_3_yl]indenyl, (5-cyclopropyl-1,2,4-oxadiazole-3-yl)methyl, [5-(difluoromethyl)_1, 2,4_17 diazole _3_yl] methyl, 5-tri-butyl-1,2,4′′diazol-3-yl)methyl, [5-(1-methylethyl H, 2,4-oxadiazoleyl)methyl, ( 4-methylhexahydropyrazine small base) fluorenyl, (3-methyl-2, yl-1,3-tetrahydro-t-s--5-yl)methyl, 2_(1_(mercaptoethyl) 143924 -sp-20091127-l ·19· 〆201020257 Aminocarbonylhexahydropyridin-3-yl)ethyl, (4-cyanopyrimen-2-yl)methyl, [5-trifluoromethyl-4-( Methyl)aminocarbonylfuran-2-yl]fluorenyl, (5-trifluoromethyl-4-aminocarbonylfuran-2-yl)methyl, [5-trifluoromethyl-4-(dimethyl) Aminomethylfuran-2-yl]fyl, [4-(cyclopropyl)aminocarbonyl_ι,3-oxazol-2-yl]methyl, (2,4-dione- 1,2,3,4-tetrahydropyrimidin-5-yl)methyl or [4-(mercaptoethyl)amino-yl-1,3-σ-[•s-2-yl]methyl; Each R4 is independently hydrogen, a gas group, a bromo group, a trifluoromethyl group, a cyano group, a 6 (diammonium) guan-3-yl group, a tetrahydrofuran _3_ group or a oxime _3_ group. Or a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention is directed to a compound of formula (ΙΠ):

Wherein: m is 1 or 2; L and M are -CH2-, and ❿ is -0-; R is nitrogen, methyl, tartar _4_ylmethyl, diphenyl fluorenyl, 4_A Oxybenzyl, sheep [word, (5-(difluoromethyl) decano-2-yl)methyl, tetrahydroindol-2-ylhydrazino, tetrahydro-2H-pyranyl-4-yl Methyl 'tetrahydro 2 Η 喊 _ 3 3 3 3 _ _ _ _ _ _ _ _ 3 3 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 Methyl '(2 external tetrahydrofuran-2-ylindenyl, tetrahydrofuran-3-ylmethyl, tetrahydrofuran-2-ylhydrazino, 3-mercaptobutyl, pentyl, 5-(methoxycarbonyl)喃-2-yl, 1'4-dioxanthene fluorenyl, [lf-based_3 (trifluoromethyl)_ιηpy 143924-sp-20091127-1

-20- 201020257 嗤·4_yl] fluorenyl, 4-methoxycarbonyl-1,3-oxazol-2-yl, 2-fluorobenzyl, 4-oxo, benzyl, 4-phenylbenzyl , (3-bromoisoxazole-5-yl)methyl, (5-exylfuran-2-yl)indenyl, propylene oxide-2-ylmethyl, (1_ethyl_1H_imidazole -5-yl)methyl, 3-cyanobenzyl, 4-cyanoindenyl, 4-(2-cyanophenyl)indolyl, 2-[(yloxy)methoxy]propyl, 2,3_Dihydro 4,4-benzodioxanthene-6-ylmethyl, 2,1,3-benzoxazol-5-ylindenyl, 2,1,3-benzo "Tomb 嗤_5_ylmethyl, (4-benzylfosfolin-2-yl)indolyl, [1-(tris-butoxycarbonyl)tetrahydropyrrol-3-yl]methyl, [(2S)-l-(Third-butoxycarbonyl)tetrahydropbipir-2-yl]methyl, hydrazine (tris-butoxycarbonyl)hexahydropyridyl]methyl, [5-( Difluoromethyl)pyran-2-yl]methyl, 峨π定_2_ylmethyl, ζμ(methylthio)-yl, (2-methoxypyrimidin-5-yl)indolyl, 2R)-l,4-dioxoindole-2-ylmethyl, 2-(2-indoleylethylidyl)ethyl, [(2s)_5-ketotetrahydrop-pyridin-2-yl] Methyl, 2-(2-keto-1,3-tetrahydrocarbazole-3-yl)ethyl 4-pyridine-2-ylbenzyl, pyrimidin-2-ylmethyl, pyrimidinylmethyl, pyridin-2-ylmethyl, (7-fluoro-1-benzofuran-2-yl) A Base, towering _3_ylmethyl, (2-ketotetrahydrocarbazol-5-yl)methyl, 3-(benzyloxy)-based, (1-methyl-1-H-benzopyrene -2-yl)methyl, 2H-benzotriazin-2-ylmethyl, 2-methoxybenzylidene, 4-methoxycarbonylthiol, 3-(benzyloxy)propyl, hexa Hydrogen says biting _4-ylmethyl, [1-(1-methylethyl) hexafluridin-4-yl]methyl, (1-ethylhexahydro? than _4_yl) methyl, ( 1-methylhexahydropyridin-4-yl)methyl, (2S)_tetrahydropyrrole-2-ylmethyl, 3-hydroxyl-yl, 2-mercapto-yl, 4-fluorenyl, 4- -(yloxy)+yl, 4-[5-(difluoromethyl)-1,2,4^diindole-3-yl], 4-(5-methyl-1,2, 4-哼二峻-3-yl)), (5-P-pyridyl-4-ylfuran-2-yl)methyl, 4-pyridin-3-ylbenzyl, (2'-biphenyl) 4-yl)methyl, 3-(5-methyl 4,2,4哼143924-SP-20091127-1 -21 - 201020257 oxazol-3-yl), 3-[5-(trifluoromethyl) )-1,2,4-dioxazol-3-yl], 4-(5-mercapto-4H-1,2,4-triazole 3-yl) fluorenyl, 3-hydroxypropyl, morpholin-2-ylmethyl, (4-mercapto-oxafolin-2-yl) fluorenyl, [4-(1-mercaptoethyl) )fosfolin-2-yl]methyl, 4-(1Η-tetrazol-5-yl)indolyl, 3-hydroxybenzyl, 4-morphobolin-4-ylbenzyl, tetrahydropyrrole-3 -ylindenyl, [1-((1-mercaptoethyl)aminocarbonyl)tetrahydropyrrol-3-yl]indolyl, [(2S)-1-methyl-5-ketotetrahydropyrrole- 2-yl]methyl, 3-(cyclohexylamino)benzyl, 3-[(2-decyloxy)amino]carbonylbenzyl, 3-[(hexyl)(methyl)amine Carboxybenzyl, 3-[(2-ethylbutyl)amino]-yl-aryl, 3-[(2,4-dimercaptophenyl)amino-decylbenzyl, 3-[( 2-phenylpropyl)amino-based benzyl, 3-[((lS)-l-cyclohexylethyl)amino]benzylidene, 3-[((lR)-l-cyclohexyl Amino]carbonylbenzyl, 2-[(4-ethylphenyl)amino]carbonylbenzyl, 2-[(2-ethylphenyl)amino]carbonylindenyl, 2-[(2 ,4-dimethylphenyl)amino]carbonylcarbonyl, 2-[(2-oximeoxyphenyl)amino]carbonylbenzyl, 2-[(2-fluorophenyl)amino]carbonylcarbonyl , 2-[(3-chlorophenyl)amino]carbonyl group, 2-[(3-fluoro-2-indenyl) Phenyl)amino-based benzyl, 2-[(heptyl)amino]hexyloctyl, 2-[(2-carbaryl)amino]carbonylcarbonyl, 2-(hexafluoropyridine-1 -yl)carbonylbenzyl, 2-[(butyl)amino]benzylidene, 2-[(3-indolylphenyl)amino]carbonylbenzyl, 2-[(2-fluoro-5) -methylphenyl)amino]carbonylbenzyl, 2-[(2,3-didecylphenyl)amino]carbonylbenzyl, 2-[(2-(4-methoxyphenyl)ethyl) Amino]carbonylbenzyl, 2-[(3-chlorobenzyl)amino]carbonylindenyl, 2-[(2-(4-phenylphenyl)ethyl)amino] ruthenyl, 4 -[(2-methoxyphenyl)aminobenzyl benzyl, 4-[(2-trifluoromethylphenyl)amino]carbonylbenzyl, 4-[(phenyl)amino]carbonyl fluorenyl 4-[(Methyl)amino]carbonylindenyl, 4-[(2-fluorophenyl)amino]carbonylbenzyl, 4-[(2-pyridin-2-ylethyl)amino] Carbonyl hydrazine 143924-SD-20091127-1 -22- 201020257 base, 4-(amino)carbonylbenzyl, 4-[(2,3-dihydro-1H-indol-5-yl)amino]carbonyl fluorenyl , 4-(morpholin-1-yl)carbonyl fluorenyl, 4-[(2-ethylphenyl)amino]carbonylbenzyl, 4-[(2,6-didecylphenyl)amino ]benzylidene, 4-[(3-fluorophenyl)amino]carbonyl Benzyl, 4-[(2,4-dimethylphenyl)amino]benzylidenebenzyl, 4-[decain-2-ylindenyl)amino]carbonylbenzyl, 4-[(B Amino]carbonyl carbonyl, 4-[(2-methoxyethyl)amino]methylidene, 4-[(2-ethoxyethyl)amino]carbonylbenzyl, 4- [(cyclobutyl)amino]carbonylbenzyl, 4-[(1,3-oxazol-2-yl)amino]carbonylcarbonyl, 4-[(3-fluoro-2-methylphenyl) Amino]carbonylbenzyl, 4-[(2-ethylbutyl)amino]carbonylbenzyl, (aminocarbonyl)methyl, [((4-ethylphenyl)amino)) ] mercapto, [((2,5-dimethylphenyl)amino)alkyl] fluorenyl, [(diethylamino) ruthenyl]methyl, [(3,3-dimethylbutyl) Amino)methyl]methyl, [(3-(1-methylethoxy)propylamino)carbonyl]methyl; [(propylamino)carbonyl]indolyl, [(phenyl)(indenyl)amine Alkylcarbonyl]fluorenyl, [((2,4-dimethylphenyl)amino)carbonyl]methyl, [((2,3-dimethylphenyl)amino)carbonyl]methyl, [( (2,6-diamidinophenyl)amino)carbonyl]methyl, (5-carboxyfuran-2-yl)methyl, [5-(dimethylaminocarbonyl)furan-2-yl]methyl , [5-(decylamine) Carbonyl)

A —furan-2-yl]fluorenyl '[4-(aminocarbonylH,3-oxazol-2-yl)indolyl, [4-((dimethylamino)carbonyl)-1,3-anthracene Zin-2-yl]methyl, 2-hydroxypropyl, (2S)-2-hydroxypropyl, 2-(benzyloxy)propyl, 2-(4-fluorobenzyloxy)propyl, 2 -(pyridin-2-yloxy)propyl, 3-hydroxybutyl, 4,4,4-trifluoro-3-hydroxybutyl, 3-aminopropyl, 3-ketopropyl, 3- [(3-methylbutyl)amino]propyl, 3-[butyl(methyl)amino]propyl, 3-[(2,2,2-trifluoroethyl)amino]. , 3-[(2-trifluoromethoxyphenyl)carbonylamino]propyl or 3-[(2-cyanoethyl)amino]propyl; 143924-SP-20091127-1 -23- 201020257 Methyl, cyano, amine, and each R6 are independently hydrogen, gas, bromo-fluoro, -C(0)H, -CH2-N(CH3)2, (tetrahydropyrrole small) Base '6 (diamine)

Stupid and pyrimido-3-yl, fluorenyl-1H_^哚_5-yl, 3,5-bis(trifluoromethyl)phenyl, 4-phenoxyphenyl, 4-(2-methylpropane Oxy)phenyl, 4-butoxyphenyl, 4-methoxyphenyl, pyrimidine-5-yl or furan-3-yl; or two R and the adjacent carbon to which they are attached form a fused a dioxanthene-thin ring or a fused ρ ratio base; a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt thereof Or prodrug. In another aspect, the invention is directed to a compound of formula (IV):

Wherein: q is 1, 2 or 3; R7 is hydrogen, (5-aero-2-Psecenyl) fluorenyl, 2-(2-methoxyethoxy)ethyl, diphenyl fluorenyl, 4-decyloxybenzyl, 3-methylbutyl, benzyl, 4-bromobenzyl, 2,3-dihydro-1,4-benzodioxene-6-ylindenyl, 2_ (trifluoromethyl)-yl, [3-(trifluoromethyl)acridin-2-yl]methyl, [5-(ra-oxy]pyridin-2-yl]indenyl, hexahydropyridine- 4-ylmethyl, (1-fluorenylhexahydropyridyl)methyl, (5-pyridylpyridin-2-yl)indolyl, [5-(trifluoromethyl)-flavor, South-_2-yl ] mercapto, (2R)-w-hydrofuran-2-ylindenyl, pyridin-2-ylindenyl, pyridinyl-3-ylhydrazino, tetragas-211-11-po--4-ylmethyl, Tetranitro-2Η-»-dean-2-ylmethyl, 143924-sp^20091127-l -24- 201020257 [ι-(2nd-butoxycarbonyl)hexahydropyridinyl]methyl, 4_anthraquinone _tetrahydropyrrole 3 based on the base or (4-methylhexahydrop to argon) methyl;

Indole-3-yloxy, amino, sulfonylamino, methanesulfonylamino, [(t-butoxycarbonyl)tetrahydropyrrole]amino, 6-methoxypyridine , 5-methyl-l'2,4-myl, amino (imido)methyl or (tetraxantrol-3-yl)amine; or two R8 groups attached to them Adjacent carbons form a copper-doped dioxo-terenyl ring, fused, a secant ring, a fused bis-quinone ring, and a fused U5_噚A oxazolyl ring, a fused tetrahydropyranyl ring, a fused 2,3-dihydropyrrole ring, a fused methyl-4,5-dihydroisoxazolyl ring Or a slightly pyridyl ring, and the remaining y groups, if present, are as described above; as stereoisomers, palmomers, tautomers or mixtures thereof; or pharmaceutically acceptable thereof Accepted salts, solvates or prodrugs. In another aspect, the invention is directed to a compound of formula (V):

Wherein: R9 is chlorine, di-p-methyl, [5-(trifluoromethyl)furanyl]methyl, (Han) tetra-furan-2-ylmethyl, pyridylmethyl, (2RH, 4_ Dioxanthene thiol 143924-sp-20091127-1 -25· 201020257 yl or (2S)-1,4-dioxoindole _2 yl fluorenyl; Or a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention is directed to a compound of formula (VI):

Wherein: Z is -Ο- or -N(H)-; R10 is hydrogen, 3-mercaptobutyl, 4-methoxycarbonyl, 2-(2-methoxyethoxy)ethyl, 4- Isoxazole _5_ylindenyl ' 2 -(trifluoromethyl)benzyl, [3 (trifluoromethyl hexyl-2-yl) fluorenyl, [4_(hydroxycarbonyl) oxazolidine_2 Methyl, [4_(N,N-dimethylamino) oxazol-2-yl] fluorenyl, (4-cyanomethylcarbonyl) phenyl, [5-(trifluoromethyl) acetyl _2_2_yl]fluorenyl, (2R)tetrahydrofuran-2-ylmethyl' (3-argyl p-bito-2-yl)methyl, [4-(indolylcarbonyl)$oxa-2-yl] Anthracenyl, 4-(3-amino-1H-ringoxime_5-yl-sermonyl, pyridin-2-ylindenyl, pyridylhydrazino or pyridin-2-ylmethyl; and R1Ga is hydrogen, Methyl or _Njj2; is a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. The invention is directed to the formula...yang compound:

143924-sp-20091127-1 •26. 201020257 where: Y is -Ο- or -S-; R11 is hydrogen, benzhydryl, 3-methylbutyl, tetrahydro-2H-pyran-4-yl Indenyl, (2R)-hydrofuran-2-ylmethyl, pyridin-2-ylindenyl or (5-chloro-1-indolyl-1H-imidazol-2-yl)methyl; Isomer, palmomer, tautomer or mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention is directed to a compound of formula (VIII):

Wherein: w is a direct bond or _ch2-; and R12 is hydrogen, a diphenylmethyl or (2R)_tetrahydrofuran-2-ylmethyl; is a stereoisomer, a palmomer, and An isomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention is directed to a compound of the formula (!Χ):

Wherein: υ is a direct bond or _CH2-; and R13 is hydrogen, diphenylmethyl, [5·(trifluoromethyl)furan-2-yl]fluorenyl or (2R)_tetrahydro-scent-2 a thiol group; 143924-sp-20091127-1 -27- 201020257 is a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate thereof or Prodrugs. In another aspect, the invention is directed to a compound of formula (X):

Is a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In another aspect, the invention is directed to a compound of formula (XJ):

Where: 乂 is -0-, _N(CH3)- or -CH2-, and Y is -N(CH3)- or -CH2-; or V is -N(CH3)- or _ch2 - ' and Y is - Ο-, _n(CH3)- or _CH2 _; and R14 is hydrogen, [5-(trifluoromethyl)indolyl]methyl, pyridin-2-ylmethyl, (: -2-yl]methyl or (state) _tetrahydrofuran-2-ylmethyl; a stereoisomer thereof, a palmo isomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, Solvate or prodrug. In another aspect, the invention is directed to a compound of formula (XII):

Of which: 143924-sp.20091127-1 -28- 201020257

R la is hydrogen or 0-pyridin-2-yl) fluorenyl; is a stereoisomer, a palmomer, a rheological isomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate thereof or Prodrugs. In another aspect, the invention is directed to a compound of formula (ΧΠΙ):

among them:

Ε is -Ο- or -CH2-; J is -〇- or -CH2-; u is a direct bond or -CH2-;

Rlb is hydrogen, [3-(trifluoromethyl) gnawed silk] methyl, diphenylmethyl or [5-(trimethylmethyl)furan-2-yl] fluorenyl, · is its apoisomer , a palmo isomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. In a further aspect, the invention is directed to a pharmaceutical composition comprising a pharmaceutically acceptable excipient, and a therapeutically effective amount of a compound of the invention as described above, a stereoisomer thereof, a palmomerisomer, A tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof. In a further aspect, the invention provides a method of treating pain in a mammal, wherein the method comprises: administering a therapeutically effective amount of a compound of the invention, as described above, to a palmomer, tautomer or Mixture, structure, sputum, academically insultable I (d) D hurried or slick music 'or pharmaceutical composition, including 143924-SP-20091127-1 -29- 201020257 == amount of the invention as described above The compound 'is a stereoisomer, a construct, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof' and a pharmaceutically acceptable excipient. In terms of the invention, the invention provides a method of treating or reducing the severity of a disease, symptom or condition in a mammal, wherein _ or a plurality of Jv 1.2, Nav U, Nav 1.4, Nav 1.5, Nav 1.6, Nav, 7 , Nay u ^ ^ 1 9 ^ activation or hyperactivity is implicated in the disease, symptom or condition, and the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of the invention as described above. a mixture of stereoisomers, palmomers, interconversions; or a pharmaceutically acceptable salt, solvate or precursor thereof, or a pharmaceutical composition comprising a therapeutically effective amount as above a compound of the present invention, which is a stereoisomer, a palmomer, an interconversion = or a mixture thereof, or a pharmaceutically acceptable salt, solvate or a steroid thereof, and a pharmaceutically acceptable compound excipient. In another aspect, the present invention provides a method of treating a disease or a condition mediated by a channel in a mammal, such as a pain associated with the treatment, a neuropathy caused by mv treatment, and a neuropathic pain. Post-harvest neuralgia, normal pain, heat sensitivity, local sarcangiosis, irritating bowel syndrome, Crohn's disease, pain associated with multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) Neuropathy, peripheral neuropathy, arthritis, rheumatoid arthritis, osteoarthritis, atherosclerosis, paroxysmal muscle tone, muscle weakness, muscle rigidity, malignant hyperthermia, gallbladder fibrosis, false Jungu Hyperketosis, rhabdomyolysis, hypogonadism, bipolar inhibition, anxiety, schizophrenia, sodium channel toxicity 143924-SP-20091127-1 •30- 201020257 Susceptibility-related diseases, familial acromegaly, Primary acral red pain, familial rectal pain, cancer, epilepsy, partial and general tension episodes, restless foot syndrome, irregular rhythm, fibromyalgia, created by stroke Neuroprotection under the state of blood must, glaucoma or nerve damage, (iv) fast

^Atrial fibrillation (four) motility and ventricular fibrosis _, wherein the method comprises administering to the mammal 'preferably humans a therapeutically effective amount, such as: 逑 the compound of the invention 'is its stereoisomer, Or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention as described Stereoisomers, palmomers, tautomers or mixtures thereof, or μ Lifei/, a scientifically acceptable salt, a solvate or a body music, and a pharmaceutically acceptable Shape agent. In another aspect, the invention provides that in a mammal, preferably a human, the soil inhibits ion flux through a voltage-dependent nanochannel in a ritual animal: a therapeutic-range channel-mediated disease or symptom A method wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount, such as: a compound 'is a stereoisomer, a palm, an isomer, a tautomer or a mixture thereof, or a An acceptable salt, solvate or prodrug pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention as described above, a helmet, a stereoisomer, a palmeoisomer Objects, interconverted structures or mixtures thereof, or medicinal herbs! " Body medicines, and academically acceptable: learn salt, solvate or excipients that are acceptable on the skin. The present invention provides a method for treating or preventing high cholesterol in a mammal, preferably a human, which comprises the method of breastfeeding having 143924-sp-20091127-1 -31-201020257 The animal is administered a therapeutically effective amount of a compound of the invention as described above, which is a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a salt of a sorghum, a 接受β ° + a solvate or prodrug, or - a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention as described above as its stereoisomer, palmomer, tautomer or Mixed with a pharmaceutically acceptable salt, solvate or prodrug thereof, and a pharmaceutically acceptable excipient. And the other aspect. The invention provides a method for treating or preventing benign prostatic hyperplasia in a mammal, preferably a human, wherein the method comprises administering a therapeutically effective amount to the desired animal. The present invention is as described above: it is not a stereoisomer, a palmomer, a tautomer or a mixture thereof: a pharmaceutically acceptable salt, a solvate or a prodrug thereof, a human peony And a therapeutically effective amount of the present invention as described above: an isomer, a palmomer, a tautomer or a pharmaceutically acceptable salt or solvate thereof Or prodrugs, and excipients that can be used in the world. The invention provides a method for the treatment or prevention of a disease in a mammal, preferably a human. The method comprises a compound of the invention as described above, in addition to a therapeutically effective amount of a stereoisomer, p s1 is a pharmaceutically acceptable A isomer, tautomer or mixture thereof, or a salt, solvate or prodrug thereof, or a compound thereof, The therapeutically effective amount of the medicinal group of the medicinal group of the invention is as described above. The present invention combines its stereoisomers, sulfonamides and the likes of the palmar isomers, tautomers or mixtures thereof, or the salts thereof. The solvate or prodrug, and the pharmaceutically acceptable 143924-SP-20091127-1 201020257 are accepted. In another aspect, the invention provides a method of treating or preventing cancer in a mammal, preferably a human, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound of the invention as described above, a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition comprising a therapeutically effective amount The above compounds of the present invention are: stereoisomers, palmomers, tautomers or mixtures thereof, or pharmaceutically acceptable salts, solvates or prodrugs thereof, and pharmaceutically acceptable Excipients. In another aspect, the invention provides a medical therapy, and in combination with - or a plurality of other compounds of the invention or one or more other accepted therapies, or any combination thereof, to increase the efficacy of the existing or untreated therapy, or to reduce the concomitant耆 Has accepted the adverse events of therapy. In a particular embodiment, the present invention relates to pharmaceuticals, <RTIgt;,</RTI><RTIgt;</RTI> Another aspect of the invention is directed to a compound of the invention as described above, which is: an isomer, a palmomer, a tautomer or a mixture thereof, or a "pharmaceutically acceptable salt, solvate or a prodrug, or a pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the invention as described above, a stereoisomer, a palmomer, a tautomer or an anthraquinone thereof, Or a pharmaceutically acceptable salt, solvate or prodrug thereof for use in the preparation of a medicament for treating a disease or condition mediated by a sodium channel in a mammal. 143924-sp-20091127-1 -33 - 201020257 DETAILED DESCRIPTION OF THE INVENTION Definitions Certain chemical groups referred to herein may be preceded by a shorthand symbol indicating the total number of carbon atoms to be found in the indicated chemical group. For example, a 2 alkyl group describes a burn group as defined below. , a total of 7 money carbon atoms 7 and the q-Cu cycloalkylalkyl group describes a cycloalkylalkyl group as defined below, having a total of 4 to 12 carbon atoms. The total number of carbons in the abbreviated symbols Does not contain the possible presence of the group described The base of carbons in addition to the above, when a request item in the specification and appended with the text, unless the contrary is specified, otherwise, the following terms have the meaning indicated: amino "means -NH2 radical. "Cyano" refers to a -CN group. "Mercapto" refers to a -C(〇)H group. The hydroxyl group '' refers to an -OH group. "Nitro" refers to a -N02 group. A keto group refers to a oxime substituent. "thiol" means a =S substituent. Difluoromethyl" means a -CF3 group. "alkane" means a straight or branched hydrocarbon chain group, which is only unsaturation of carbon and hydrogen atoms, and has from 1 to 12 carbon atoms preferably from _ to eight < atom or - to six carbon atoms, which are linked by a single bond] the rest of the molecule 'eg methyl, ethyl, n-propyl, i methyl ethyl (i) propyl) n-butyl, n-pentyl Base, u dimethylethyl (t-butyl), : 143924-sp-20091127-l 201020257 methylhexyl, 2-methylhexyl, etc. Unless otherwise specifically stated in this patent specification, the alkyl group is visible The situation is replaced by one of the following groups: alkyl, alkenyl, indenyl, haloalkenyl, cyano, nitro, aryl, cycloalkyl, heterocyclyl, heteroaryl, keto, trimethylnonane Base, _〇r40, _〇c(〇>r40, _n(r40)2, -C(0)R4〇, _c(0)OR4〇, -C(O)N(R40)2, _n(R40 C(O)OR42, -N(R40)C(O)R42, -N(R40)S(〇)tR42 (where t is J to 2), _s(〇)t〇R42 (where t is 1 to 2), -S(0)pR42 (where p is 〇 to 2) and _s(〇)tN(R4〇)2 (where t is 1 to 2), wherein each r4 〇 is independently hydrogen, alkyl, Haloalkyl a cycloalkyl group, a Φ cycloalkyl group, an aryl group, an arylalkyl group, a heterocyclic group, a heterocyclic alkyl group, a heteroaryl group or a heteroarylalkyl group; and each R42 is an alkyl group, a haloalkyl group or a cycloalkane group Alkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl. "alkenyl" means a straight or branched hydrocarbon chain radical, It consists solely of carbon and hydrogen atoms, contains at least one double bond, has two to twelve carbon atoms, preferably one to eight carbon atoms, and is linked to the rest of the molecule by a single bond, for example, Dilute, prop-1-enyl, butenyl, pent-1-enyl, pentane 4,4-diphenyl, etc. Unless otherwise stated in this patent specification, the dilute base may be as follows Substituted one of the groups: alkyl, alkenyl, halo, alkenyl, cyano 'nitro, aryl, cycloalkyl, heterocyclyl, heteroaryl, keto, trimethyl sulphate, - 〇R40, -〇C(〇)_R40, _n(r40)2, _c(〇)r4〇, -C(0)〇R4〇> -C(〇)N(R4〇)2 ^ -N(R40 C(O)OR42 ^ -N(R4 0)C(〇)R4 2 , -N(R4〇)S(0)tR42 (where t is 1 to 2), -S(0)t0R42( Where t is i to 2), _S(〇)pR42 (where P is 〇 to 2) and -S(0)tN(R4〇)2 (where t is i to 2), wherein each R40 is independently hydrogen, Alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, 143924-sp-20091127-l •35· 201020257 aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or hetero Aralkyl; and each R42 is alkyl, dentate, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl . The extension or base chain " refers to a straight or branched bivalent hydrocarbon chain that links the rest of the molecule to a group, consisting only of carbon and hydrogen, does not contain unsaturation, and has one to ten Two carbon atoms, such as anthracene, ethyl, propyl, n-butyl and the like. The alkyl chain is attached to the remainder of the molecule via a single bond and through a single bond to the group. The alkyl chain can pass through one or both of the carbons in the remainder of the molecule and the point of attachment to the group. Unless specifically stated otherwise in this patent specification, an alkylene chain may be optionally substituted with one of the following groups: alkyl, alkenyl, self-group, alkenyl, cyano, nitro, aryl, naphthenic Base, heterocyclic group, heteroaryl group, keto group, trimethyl decyl group, -OR4 0, _〇C(〇)_R4 0, _n(r4〇)2, _c(〇)r4(), _c(〇 ) 〇r40, -C(O)N(R40)2 x -N(R40)C(O)〇R42 ^ -N(R40)C(O)R42 > -N(R40)S(O)tR42 ( Where t is 1 to 2), -S(0)t〇R42 (where t is 1 to 2), -S(0)pR42 (where p is 0 to 2), and -S(0)tN(R4〇) 2 (wherein t is χ to 2), wherein each r4 oxime is independently hydrogen, alkyl, dentyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclyl Or an alkyl group, a heteroaryl group or a heteroarylalkyl group; Heteroaryl or heteroarylalkyl. "Extend alkenyl" or "alkenyl chain" means a straight or branched divalent hydrocarbon chain which links the remainder of the molecule to a group consisting solely of carbon and hydrogen and containing at least / double bonds And having one to twelve carbon atoms, such as a vinyl group, a dilute base, a n-butenyl group, and the like. The dilute base chain is attached to the molecule via a single bond 143924-sp-20091127-1 -36- 201020257 and the remainder' and via a double bond or a single bond to the group. The extended alkenyl chain may pass through a carbon or any two carbons in the chain to the remainder of the molecule and to the point of attachment to the group. Except as otherwise specifically stated in this patent specification, the extended chain may be optionally substituted by one of the following groups: alkyl, alkenyl, dentyl, haloalkenyl, cyano, nitro, aryl, naphthenic Base, heterocyclic group, heteroaryl group, keto group, tridecyl decyl group, _〇R4〇, _〇C(〇)_R40, _N(R40)2, _c(〇)r40, -C(0)OR40 , -C(O)N(R40)2, -N(R40)C(O)OR42, _N(R40)C(O)R42, -N(R4G)S(0)tR42 (where t is i to 2 ), -S(0)t0R42 (where t is 1 to 2), ❹ _S(0)PR42 (where P is 0 to 2), and -S(O)tN(R40)2 (where t is 1 to 2) Wherein each R4Q is independently hydrogen, alkyl, _alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroaralkyl And each R42 is alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl. ^Base means a hydrocarbon ring system group comprising hydrogen, 6 to 18 carbon atoms and at least one aromatic ring. For the purposes of the present invention, an aryl group can be a monocyclic, double bicyclic, tricyclic or tetracyclic ring system which can include a fused or bridged ring system. The aryl group includes, but is not limited to, derived from terpene, terpene tea, pet phenanthrene, anthracene, lin, benzene, grotto, sputum, sputum, as_莽 leather, s· although |, sputum, sputum, sputum, Anthracene, phenanthrene, T, anthracene and aryl of benzophenanthrene. Unless specifically stated otherwise in the specification, an aryl group may be optionally substituted with one or more substituents. The substituents are independently selected from the group consisting of alkyl, dilute, halo, dentate, halo. Alkenyl, cyano, nitro, aryl, aryl, cyclo, cyclohexyl, heterocyclyl, heterocyclyl, heteroaryl, heteroaryl, -R41-OR4〇 , -R41-OC(0)_R4〇, _r41_n(r40)2, _r41_c(〇)r4〇, 143924-sp-20091127-1 -37- 201020257 -R41-C(O)N(R4 0)2, , - ruler 41 - wind ruler 40) 5 (〇) #2 (where 1 is 1 to 2), , -R41-S(0)t0R42 (where t is 1 to 2), -R41-C(O)OR4 0 x _rA - R41-N(R40)C(〇)R4 2, -R41-N=C(OR4〇)R4〇, alkyl group. _R41 _S(〇)pR42 (wherein P is 0 to 2) and -R41 -S(O)tN(R40)2 (where t is i to 2) wherein each R4 oxime is independently 氲, alkyl, dentate , cycloalkyl, cycloalkylalkyl, aryl 'aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or hetero-aromatic, each R is independently a direct bond or a straight chain or a minute a branched or extended alkenyl chain; and each R42 is alkyl, _alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, hetero An aryl or heteroaryl-''aralkyl'' refers to a radical -Rb-heart group, wherein Rb is an alkylene chain as defined above, and Rc is one or more aryl as defined above, for example Mercapto, diphenylmethyl and the like. The alkyl chain portion of the aralkyl group may optionally be substituted as described above for the alkyl chain. The aryl moiety of the aralkyl group can be optionally substituted as described above for the aryl group. "Cycloalkyl" means a stable non-aromatic monocyclic or polycyclic hydrocarbon group consisting solely of carbon and hydrogen atoms, which may comprise a fused or bridged ring system having from ❹ to fifteen carbon atoms. Preferably, the system has three to ten carbon atoms and is saturated or unsaturated and is attached to the remainder of the molecule by a single bond. Monocyclic groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl. , cyclohexyl, cycloheptyl and cyclooctyl. Polycyclic groups include, for example, gold alkyl, n-fosino, decaenyl, 7,7-dimethyl-bicyclo[2.2.1]heptyl Etc. Unless specifically stated otherwise in this patent specification, a cycloalkyl group may be optionally substituted with one or more substituents. The substituents are independently selected from the group consisting of alkyl, dilute, 143924-SP- 20091127-1 -38- 201020257 Halo, _alkyl, halogen, cyano, schiffki, steel, aryl, aryl, cycloalkyl, cycloalkylalkyl, heterocyclic, heterocyclic Alkyl, heteroaryl, heteroarylalkyl, -R41-〇R4〇, _R41_〇C(〇)_R40, _r41_N(R40)2, -R4 1 -C(0)R4 °, -R4 1 -C (〇)〇R4., -R4 1 _c(9)N (R4 0 )2, _R4 1 _N(R4 0 )c(〇) OR4 2, -R4 1 -N(R4 0 )C(0)R4 2, -R4 1 -N(R4 0 )s(0)t R4 2 (where t is 1 to 2), -R41-N=C(OR4〇)R4〇, _R4i_s(0)t〇R42 (where t is ! to 2), 2), where each R4 is independent Hydrogen, alkyl, haloalkyl, cycloalkyl, naphthylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroarylalkyl; each R4i is independent a direct bond or a linear or branched alkyl or extended alkenyl chain, and each R42 is an alkyl group, a haloalkyl group, a cycloalkyl group, a cycloalkylalkyl group, an aryl group, an aryl group, a heterocyclic ring. a cyclyl group, a heteroaryl group or an alkyl group. ❹ "cycloalkyl group" refers to a RbRg group, wherein the alkyl group is as defined above and Rg is a ring as defined above. Burning base. The extension can be replaced as defined above. Inventive 1 thickened material = any of the ring systems described herein, which are slightly bonded to the present: in:: an existing ring structure. When the fused ring system is a heterocyclic or heterocyclic group, it becomes the condensed. Any carbon can be replaced by nitrogen. The part of the existing ring structure of money - the letter base, refers to the Xiji, gas base, Dunke or the barrier. The i-based system refers to a dentate group as defined above, a dentate group as defined herein, for example, a trifluoromethyl group, a fluoromethyl group, or a plurality of the above 2,2,2-trifluoroethyl, j-fluorogan^ Soil monochloromethyl, ^ fluoroethyl, 3_glycol-2-fluoropropyl, 143924-sp-2009U27-l -39- 201020257 parts can be as above 1-sided methyl-2-bromo S Ethyl and the like. The alkyl moiety of the geminyl group is substituted with respect to the alkyl group. "Heterenyl" refers to a dilute group as defined above which is substituted by or a plurality of halo groups as defined above. The dilute moiety of the indenyl group may be optionally substituted as defined above for the dilute group. ''Heterocyclyl'' means a stable 3 to 18-membered non-aromatic ring group containing from two to twelve carbon atoms and one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur The heterocyclic group may be a mono-, bicyclic, tricyclic or tetracyclic ring system, which may comprise a fused or bridged ring system, unless otherwise specifically stated in this patent specification; And the nitrogen, carbon or sulfur atom in the heterocyclic group may be oxidized as appropriate; the nitrogen atom may be quaternized as appropriate; and the heterocyclic group may be partially or fully saturated. Examples of such a heterocyclic group include, but are not limited to, Dioxinyl phenyl [1,3] dithiorepine, decahydroisoinyl, diazoxide, tetrahydroimidazolyl, isoxazolidinyl, isotetrahydrocarbazolyl, Florinyl, octahydroindenyl, octahydroisoindolyl, 2-ketohexahydropyrrole, 2-ketohexahydropyridyl, 2-ketotetrahydropyrrolyl, tetrahydrocarbazole , hexahydropyridyl, hexahydropyridinyl, 4-hexahydropyridinyl, tetrahydropyrrolyl, tetrahydropyrazolyl, fluorenylpyridyl, thiazolidinyl, tetrahydrofuranyl, trioxoyl-trisulphur Sulfhydryl, tri-n-alkyl, tetrahydropyranyl, thiomorpholine, thio-homofolinyl 1-keto-thiofenofyl and i,i-diketo-thio Fulinski. Unless otherwise expressly stated in this patent specification, a heterocyclic group may be optionally substituted with one or more substituents selected from the group consisting of alkyl, dilute, south, halogen. Anthracenyl, haloalkenyl, cyano, keto, thioketo, schlossyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclic 143924-sp-2〇〇91127 -1 -40- 201020257 aryl group, heteroaryl group, heteroaryl group, -R41-〇R4〇, _r4 1_〇c(〇)-R40, -R4l-N(R4〇)2, _r4 1_C( 〇) R4(), _R41<:(〇)〇r4., _r41_c(〇)n(r40)2, 'R41'n(r40)C(O)OR42 ' -R41-N(R40)C(O) R42 ' -R41-N(R40)S(O)tR42 (where t is 1 to 2), -R41-N=C(OR40)R40, _R4i_s(0)t0R42 (where t is 1 to 2), -R41 -S(0)pR 42 (wherein p is 〇 to 2) and -R41-S(〇)tN(R40)2 (where t is 1 to 2)' wherein each r4 oxime is independently hydrogen, alkyl, dilute, orchiral, a cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl or heteroaryl group; each r4i is independently a direct bond or a straight chain or a branched alkyl or an extended alkenyl chain; and each R42 is alkyl, alkenyl, dentyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocycloalkyl Base, heteroaryl or heteroaryl. "Ν-Heterocyclyl" means a heterocyclic group as defined above containing at least one nitrogen. The fluorene-heterocyclic group may be optionally substituted as described above for a heterocyclic group. "Heterocyclylalkyl" a radical of the formula -RbRh, the center of which is an alkylene chain as defined above, and Rh is a heterocyclic group as defined above, and if the heterocyclic group is a heterocyclic group containing a t-heterocyclic group, the heterocyclic group may be bonded The base is on the nitrogen atom. The alkyl chain of the heterocyclylalkyl group can be optionally substituted as defined above for the alkyl chain. The heterocyclic moiety of the heterocyclic base group may be optionally substituted as defined above for the heterocyclic group. "Doped aryl" means a 5- to 14-membered ring system group comprising a gas atom, one to thirteen carbon atoms, one to six heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur' and at least An aromatic ring. For the purposes of the present invention, a heteroaryl group can be a monocyclic, bicyclic, tricyclic or tetracyclic ring system containing a fused or bridged ring system; Any nitrogen or carbon in the aryl group or 143924-SP-20091127-1 -41 - 201020257 The sulfur atom may be oxidized as appropriate; the nitrogen atom may be quaternized as appropriate. Examples include, but are not limited to, a nitrogen hepta-alkenyl group, acridine Benzoimidazolyl, benzopyrazolyl, benzindenyl, benzodioxolanyl-benzofuranyl, benzoxazolyl, benzothiazolyl, benzoxadiazole Benzene [i,4]dioxygen ytterbium-based benzophenoxydioxanyl benzoxanthyl, benzoxazolyl, benzodioxolanyl, benzo Dioxetolyl, benzopipetanyl, benzopentanyl, benzofuranyl, benzofuranone, benzothienyl (benzothiophenyl), benzotriazolyl, benzene And [4,6 Imidazopyridyl, benzoxazolone, benzimidazolium, carbazolyl, fluorenyl-benzofuranyl, dibenzophenylthio, cumyl, furanone , isoxazolyl, imidazolyl, carbazolyl, fluorenyl 'carbazolyl, isodecyl, indanyl, isoindolinyl, isoquinolinyl, hydrazine, isoxazole Base, acridinyl, oxadiazolyl, 2-nitrox-7-nonenyl, oxazolyl, oxiranyl, 1-oxypyridyl, oxypyrimyl, i-oxypyrylene, 1-oxidation嗒耕基, μphenyl_1H_pyrrolyl, phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl phenyl Pyridyl-pyridinone, pyridinyl, pyrimidinyl, pyrimidinone, © hydrazine, pyrrolyl, pyrido[^-pyrimidinone, quinazolinyl, quinazolinone, quinoxalinyl , quinoxalinone, quinolyl, isoquinolyl, tetrahydroquinolyl, pyrazolyl, pyrimazolyl, pyrimido[3,2_d]pyrimidinone, cumene [2, 3-d]pyrimidin-4-one, triazolyl 'tetrazolyl, tri-farming and thiobenzene (i.e., ϊ»塞基基). Unless specifically stated otherwise in the specification, a heteroaryl group may be optionally substituted with one or more substituents selected from the group consisting of alkyl groups, Alkenyl, functional group, _alkyl, alkenyl, cyanide 143924.sp.20091127-1 -42* 201020257 base, keto group, thioketo group n, thioketo group, aryl group, aryl group, cycloalkyl group , cycloalkyl, heterocyclic, heterocyclic, tetrakis, heteroaryl, -R41-OR4, -R4l_〇C(9)_R4 0, _R4 1_N(R4, _r41_c((7)r4〇, 'r41 'C(0)0r4° ' -r41-C(O)N(R40)2 . -R4^^^0)0(0)0^2 . -R41-N(R4 0)C(O)R42, _r41_N(r4〇) ah r42 (where [for [to 2], KN=c(ORn _R41_s(〇)t〇R42 (where t is 1 to 2), _R41 -s(0)p R4 2 (where P is 0 to 2) and -R41 -s(0)t N (R4. )2 (where t is i to

2) wherein each R4 oxime is independently hydrogen, alkyl, alkenyl, dentyl, cycloalkyl, cycloalkyl, aryl, aryl (tetra), heterocyclic, heterocyclic, heteroaryl Or a heteroaromatic group; each R41 is independently a direct bond or a straight or branched extension or an extended alkenyl chain; and each r42 is a substituent, an alkenyl group, a halogen group, a cycloalkyl group, a ring A hospital base, an aryl group, an aromatic group, a heterocyclic group, a heterocyclic group, a heteroaryl group or a heteroaryl group. "N-heteroaryl refers to a heteroaryl group as defined above containing at least one nitrogen, and wherein the point of attachment of the heteroaryl group to the remainder of the molecule is through the nitrogen atom in the heteroaryl group. It may be substituted as described above for the heteroaryl group. • "Iheteroaryl" means (RbRi, wherein Rb is alkyl as defined above and Ri is heteroaryl as defined above. The heteroaryl portion of a heteroarylalkyl group may be as above The substituted alkyl group of the heteroaryl group may be substituted as defined above with respect to the alkyl chain. "Hydroxyalkyl" refers to the formula _Rb〇H group, Wherein Rb is any carbon in which the OH group of the exo-system bond as defined above may be attached to the exfoliation bond. The portion of the exfoliation chain of the heteroaromatic group may additionally be as defined above with respect to the extension bond 143924. -sp-20091127-1 •43- 201020257 Replacement of the righteousness. "Analgesic method" means that the pain that is painful under normal circumstances is not in the pain. "Feeling abnormality" refers to the perception that it is harmless under normal circumstances, such as stress. Or a slight contact, is perceived as a symptom of extreme pain. "Prodrug" is intended to mean a compound that can be converted to a biologically active compound of the invention under physiological conditions or by solvolysis. Therefore, "prodrug" The term "the compound of the invention" a metabolic precursor which is pharmaceutically acceptable. The prodrug may be inactive when administered to a patient in need thereof, but is converted in vivo to the active compound of the invention. Prodrug blood group: Rapid transformation in vivo produces the parent compound of the invention, for example via hydrolysis in the blood. Prodrug compounds often provide solubility, tissue compatibility or delayed release advantages in mammalian organisms (see B_gard, H) "Design of Prodrugs (1985), pp. 7, 9124

Amsterdam)). The discussion of prodrugs is provided in the TCM, τ et al. "Prodrugs as a novel delivery system,", ACS. The series, the first call, and the bioreversible carrier in drug stun, Edward Β · R〇 Edited by Che, American Medical Association and Pergamon Press, Cong's both are hereby incorporated by reference. "Prodrugs are also meant to include any covalently bonded carrier when such prodrugs are administered In a mammalian condition, it releases the active compound of the present invention in vivo. The prodrugs of the compounds of the present invention can be prepared by modifying the functional groups present on the compounds of the present invention in such a manner as to cause such modifications. Is a parent compound that is cleaved, in routine operation or in vivo. Prodrugs include compounds of the invention wherein 143924-SP-20091127-1 201020257, an amine-based group binds to any group, #本When the invented compound drug is administered to a cow disease animal, it will be divided into: a hydroxyl group, a free amino group or a free state thio group. The prodrug is not limited to the vinegar of the alcohol functional group in the compound of the present invention. , a = benzoate derivative, or a amide derivative of an amine functional group, etc. The invention disclosed herein also means that all pharmaceutically acceptable compounds encompassing the invention are identified isotopically, The method is such that the atoms of the group are replaced by atoms having different atomic mass or mass. Examples of the isotopes which can be incorporated into the disclosed compounds include hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, chlorine and iodine, such as 2h, 3h, 11c, 13c: 14c13ni5 15〇, 17〇, 18〇, 31p, 32p, 35s, 18F, 36ci,, a marker compound can be used to help determine or measure the effectiveness of a compound, for example by characterization of sodium. The position or mode on the channel, or the binding affinity for a pharmacologically important position on the sodium channel. Certain compounds of the invention that are labeled isotopically, such as those incorporating a radioisotope, can be used for drugs and/or substrates. Tissue distribution study. Radioactive isotope 氚, yellow ie 'with carbon _14, meaning 14C 'in its easy to incorporate and immediately ^ test ^ set' is particularly useful for this project. Isotopic substitution, such as 2H, may provide certain therapeutic benefits due to greater metabolic stability, such as increased in vivo half-life or reduced dosage requirements, and thus may be preferred in some circumstances. Substitution with anodic electron emission isotopes, such as nC, i8P'15〇 & 13N, can be used for positron emission surface morphology (PET) studies to test for acceptor receptors 143924-sp-20091127-l •45- 201020257. The method of the invention is also known as the compound of the present invention. The conventional techniques known to the artist can also be used in the method described in the recipe, using the appropriate examples and preparations. The unrecognized test used in the reagent substitution game was made. W replaces the intrinsic metabolites of the invention disclosed herein. Such a product can be used for the in vivo use, reduction, hydrolysis of the compound, oxidation of the compound to be administered, hydrazylation, esterification, etc., which are mainly caused by the enzyme process. Therefore, the present invention includes a compound produced by a process, and the compound of the present invention is used to contact the compound of the present invention with a mammal, and after a period of time, it is produced by The time of the product. Such products are typically presented in the following manner: 'The radiolabeled compound of the invention is administered to the animal at a detectable dose, such as a rat, a mouse, a guinea pig, a monkey or a human, to allow sufficient time. Metabolic effects occur and the conversion products are isolated from urine, sputum or other biological samples. "Stabilizing compounds" and "stabilizing structures" are intended to mean a compound that is sufficiently robust to survive from the reaction mixture, to a useful purity, and to be formulated into an effective therapeutic agent. "Mammals" Domestic animals, such as laboratory animals and family pets (such as tracing, dogs, pigs, cows, mutton, goats, horses, rabbits), and non-domestic animals such as wild animals, etc. Use or as appropriate The described event or condition may or may not occur 'and the description includes the circumstances in which the event or condition occurred and the circumstances in which it did not occur. For example, " optionally substituted aryl, means aryl can be or It may be unsubstituted, and the description includes the substituted 143924-sp-20091127-1 -46- 201020257 aryl group and the unsubstituted aryl group. When the functional group is described as v, as the case may be taken p, and in turn The substituent on the functional group is also "optionally substituted" and the like, for the purposes of the present invention, such an iteration is limited to five. ''Pharmaceutically acceptable load Agents, diluents or excipients include, but are not limited to, any adjuvants, carriers, excipients, glidants, sweeteners, diluents, '^ preservatives, dyes/colorants, bridge flavor enhancers , surfactants, wetting agents, dispersing agents, suspending agents, stabilizers, isotonic agents, solvents or emulsifiers, which have been approved by the U.S. Food and Drug Administration to be acceptable for use in humans or livestock Φ animals. "Pharmaceutically acceptable salts" include both acid and base addition salts. "Pharmaceutically acceptable acid addition salts" means salts which retain the biological effectiveness and properties of the free base and which are not biologically It is undesired or otherwise formed, and is formed with inorganic acids such as, but not limited to, hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc., such as, but not limited to, acetic acid, and organic acids. 2,2_di-gas acetic acid, adipic acid, alginic acid, _ascorbic acid, aspartic acid, benzenesulfonic acid, benzoic acid, 4_acetamidobenzoic acid® camphoric acid, camphor-10-continued acid, Capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclohexane aminosulfonic acid, dodecyl sulfuric acid, ethane disulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, citric acid , fumaric acid, galactose diacid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, face acid, valeric acid, 2-keto-glutaric acid, glycerol citrate, ethanol Stuffing, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, cis-succinic acid, malic acid, malonic acid, Glycolic acid, methane acid, galactose diacid, sulfonium disulfonic acid, indole-2-acid, i_hydroxy-2-indolecarboxylic acid, nicotinic acid, oleic acid, whey 143924-sp-20091127-l • 47· 201020257 Acid, oxalic acid 'palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4-aminosalic acid, sebacic acid, stearic acid, acr (tetra), tartaric acid, sulfur Cyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, decanoic acid, and the like. "Pharmaceutically acceptable base-addition salt" means a salt that retains the effective danger and properties of the free-acid organism, which is not biologically or otherwise undesirable. These salts are self-adding inorganic Or organic test to free acid. Salt derived from inorganic test, including but not limited to sodium, _, bell, ammonium, #5, magnesium, iron copper M, Shao salt, etc. The preferred inorganic salt is bell, nano , unloading, handling and locking of salt from organic testing, including but not limited to the following salts, a ', grade and - amines, substituted amines, including naturally occurring substituted amines cyclic amines And anionic ion exchange resins, such as ammonia, isopropylamine, methylamine-ethylamine, diethylamine 'tripropylamine, diethanolamine, ethylamine, monomethylolethanol, 2-dimethylaminoethanol, 2nd diethyl Aminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, t-rucaine, seabamine, choline, betaine, benzidine, benzathine, B Diamine, glucosamine, methyl glucosamine, cocoa, triethanolamine, succinylamine, ^ octahydropyridyl 'hexahydropyridine, hydrazine Ethyl hexahydropyridine, polyamine resin, etc. The best organic test is isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline and caffeine. Usually, crystallization will produce the compound of the present invention. Solvate. As used herein, the term "solvent" refers to an aggregate comprising one or more molecules of the compound of the invention and - or a plurality of solvent molecules. The solvent may be water, in such a case, The lozenge may be a hydrate. Alternatively, the solvent may be an organic solvent. SU匕, the compound of the present invention may be present as a hydrate, including monohydrate 143924-SP-20091127-1 -48- 201020257, hydrate, hemihydrate, The sesquihydrate 'trihydrate, tetrahydrate = et al' and its corresponding solvated forms. The compounds of the invention may be true cold hydrates, while in other instances, the compounds of the invention may simply retain sporadic water or A mixture of water and a portion of an incidental solvent. *Pharmaceutical composition means a medium of the present invention which is generally used in the art and which is used to transport a biologically active compound to a mammalian such as a human. Include all pharmaceutically acceptable carriers, diluents or excipients for their use. The therapeutically effective amount " refers to the amount of the compound of the invention when it is administered to a mammal, preferably a human. A treatment sufficient to cause a disease or symptom in a mammal, preferably a human, as defined below. The composition of the compound of the invention is based on the compound, the symptoms and the manner in which it is administered. And the age of the mammal to be treated, = can be routinely determined by the artist's own knowledge content. "Introduction, bottom, ancient jade treatment or "Treatment" includes a disease or condition of interest in a mammal having a human disease or condition of interest, preferably a human, and includes: ^ preventing the disease or symptom from occurring in the mammal, especially When such a Nanli animal is susceptible to the symptoms, but the Wo is cut off to have the disease; inhibiting the disease or symptom means to curb its development; or (4) relieving the disease or symptom, meaning that the disease or symptom is degraded. Since ⑼ alleviate symptoms of the disease or symptoms caused it, which means to alleviate pain 143924-sp-20091127-1 • 49- 201020257 pain without focusing on the subordinate's disease or symptoms. The term "disease" and "symptom" as used herein are used interchangeably or may be different in that the particular disease or condition may not have a known causative agent (so that the etiology has not been studied), and thus Not yet considered a disease, but only an undesired symptom or symptom box, in which a more or less specific combination of symptoms has been confirmed by the clinician. The compound of the present invention or a pharmaceutically acceptable salt thereof may contain - or more than The center of symmetry' and thus the palmier isomers, diastereomers and other stereoisomeric forms, which can be defined by absolute stereochemistry, are defined as ❹ or (7)-' or by amino acid Or (L)_. The invention is meant to include all possible isomers, as well as their racemic and optically pure forms. Optically active (+) and (-), (8)- and (5> or (D) The _ and (L) _ isomers can be prepared using palmar synthetic units or palmitic reagents, or resolved using conventional techniques, such as chromatography and fractional crystallization. Preparation/single separation of individual pairs of isomers Techniques, including the synthesis of purely precursors from appropriate optics, or The resolution of the racemate (or a substance other than a salt or a derivative) is such that (4) is as in the case of high pressure liquid chromatography (HPLC). When the compounds described herein contain olefinic double bonds or other geometric ❹ asymmetry "At the center" and unless otherwise specified, such compounds are intended to include both E and Z geometric isomers. Similarly, 'all tautomeric forms are also intended to be included. "Stereoisomer" means the same atom Compositions, which are bound by the same bond but have different secondary structures, are not interchangeable. The invention is intended to cover various stereoisomers and mixtures thereof, and includes " palmar isomers" Stereoisomers whose molecular systems are non-superimposable mirror images of each other. 143924-sp-20091127-1 -50- 201020257 Submutation - isomers means that protons are transferred from one atom of the molecule to the same. Atom. The invention includes any tautomer of the compound. 'Also within the scope of the invention, the keeper is an intermediate compound of the invention, and all polymorphs of the above-mentioned & Crystallized

'The chemical naming scheme and structure diagram used in the text is the modified form of the I.U.P.A.C. naming system'. The use of the bribe named version 9.07 software program, wherein the compound of the present invention is a derivative of the core structure of the towel. The complex chemical name 'substituent' as used herein is referred to before the group to which it is attached. For example, an anthracenylethyl group contains an ethyl main chain having a cyclopropyl group. All bonds are confirmed in the chemical structure diagram, except for some carbon atoms that are sufficiently hydrogen atoms to complete the valence bond. Thus, for example, a compound of formula (I) as taught above in the Summary of the Invention, wherein n is 1, J is an even-' ruler-〇-12 is hydrogen, and 1^ is (L. tetrahydrofuran-2-ylindole) Base; meaning compound of the formula:

It is called in this article! , if, hydrogen benzophene-2-ylmethyl]_4H snail [biting ^ ^ [3'2-g] [l, 3] benzodioxene _6,3, _10]_2, ( 1, η)·嗣. DETAILED DESCRIPTION OF THE INVENTION A specific embodiment of the invention is a compound of formula (I) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is where _0_,

143924-SP-20091127-1 -51 - 201020257 and K is -CH2 - a compound of formula (I). In this particular embodiment, a specific embodiment is a compound of formula 1, selected from the group consisting of: fluorenyl-mercapto- 21 keto-N-pentyl m3-tetrahydrospiro [, succinyl [2, 3 g] [ l 4] benzodioxanthene oxime] W-carboxamide; 1 - (monophenylmethyl)-4,6-monomethoxy-2,3-dihydrospiro [sniffin [2, 3414] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-_ ; (8R)-r-[(2R)-l,4-dioxoindole-2-yl Methyl]_2,3_dihydrospiro[furo[2,3-g][l,4] benzo-oxo-salt -8,31^丨嗓] ketone; 1 -[(6-曱Base p is more than 2-yl)methyl]-2,3-dihydrospiro [biting and arranging [2,3_g, 4] benzodioxanthene-8,3'-吲哚]-2 '(1'11)-ketone; Γ-(pyridin-3-ylmethyl)-2,3-dihydrospiro [bito-and-[2,3-g][i,4]benzodioxan Alkene-8,3'-吲哚]-2'(1Ή)-one; (11)-3,7-dihydro-211-spiro[benzopyrano[5,6-7][1,4] Dioxoenene-8,3,-dihydroanthracene-2'-one; (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzene Dioxane hydrazine _8,3'_Ρ5丨哚]-2'(1Ή)-ketone; (8S)-l'-{[3-(Tris-decyl)pyridin-2-yl]indole 2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene _8,3'_蚓]_2'(ΓΗ)-ketone; (8S)-l'-[(5-pyridyl-2-yl)indolyl]_2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene-8,3,-蚓哚]-2,(1Ή)-one; Γ-[(5-bromopyridin-2-yl)methyl]-2,3 - dihydrospiro[furan P,3-g][l,4] benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one; Γ-(diphenylmethyl) )-2,3-dihydrospiro[[,,,,,,,,,,,,,,,哚]-2,(1Ή)-ketone; 6'-isopentyl-3,7-dihydro-2Η-spiro[benzopyrano[5,6-b][l,4]dioxane Alkenyl-8,8'-pyrazolo[5,4-6]indole-7'(6'11)-one; 6-((5-(trifluoromethyl)methane-2-yl)曱))-2,3,3·,7·-tetrahydro-2Ή-spiro[[1,4]dioxoisenene[2,3-fH丨哚-8,8'-benzofuran [5,6-b][l,4]dioxolysene]-7(6H)-one; 2,3-dihydrospiro[2,3-g][l,4]benzene Dioxetemene _8,3,_H丨嗓]_2, (γη) ketone; ❹ 1 -(3-mercaptobutyl)-2,3-one wind snail [ρofran[2, 3-g][l,4]benzodioxanthene -8,3'-啕嗓]-2·(1Ή)-one; Γ-(®Hex-2Η4 "South_4_ylmethyl )_2,3-dihydrospiro Fusino[2,3-g][l,4]benzo-y-milk orthorhombic-8,3Ή|p to]-2*(1'H)-net; 1'-(tetrahydro-2H -piperidin-2-ylmethyl)-2,3-dihydrospiro-dea-[2,3-g][l,4]benzo,monooxindole p-][*](1 'H)·嗣; l'-[(5-Alkyl-1-methyl-1H-imidazol-2-yl)indenyl;]_2,3-dihydrospich-[2,3-g ][l,4]benzodioxanthene _8,3'_, 嗓]_2'(i,h) ketone, ® 斤 chloromethyl-1·methyl_1H_imidazole-2 -yl)f-based]_2,3-dihydrospiro[ollenyl[2,3-g][l,4]benzodioxolene _8,3·_ρ5 bud]-^, ketone Hydrochloride; 1-(pyridin-2-ylmethyl)-2,3-dihydrospiro[c-buto[2,3_g][1,4]benzodioxanthene_8,3%哚]_2·(ι·η)-_ ; 1·-〇pyridin-2-ylindenyl)-2,3-dihydrospiro[吱,[2,3_g][1,4]benzoic Oxadecene-8,3'-吲哚]-2'(1Ή)-_hydrochloride; 1 -[(2S)-rahydrofuran-2-ylindenyl]_2,3-dihydrospiro[吱和[2,3_g][14]benzodioxanthene-8,3·-啕嗓]·2,(1Ή)-_ ; 143924-sp-20091127-1 -53- 201020257 Γ-_ - Tetrahydrogen bite. Nan-2-ylmethyl]-2,3_dihydrospiro[吱,[2,3 g][i,4] benzodioxanthene-8,3·-吲哚]-2·( 1Ή)-_ ; 1'-(1,4-Dioxaindole-2-ylmethyl)-2,3-dihydrospiro [cough and [2,3 g][1,4]benzoic Oxalene-8,3'-吲哚]-2'(1Ή)-one; Γ-(3'4-dimethoxybenzyl)_2,3-dihydrospiro[furo[2,3 §][1,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; Γ-(3,5-didecyloxy)_2,3_ Dihydrospiro[furo[2,3 g][1,4]benzodioxolene-8,3·-吲哚]-2·(1Ή)-one; 1'-(2,3- Dinitro-1,4-benzodioxanthene _6·ylmethyl)2 3_digas snail [cough merging [2,3-g][l,4] benzo-oxygen -8,3^3⁄4丨嗓]_2'(i'h)-ketone; (8)-Γ-{[5-Ρfluoromethyl)pyran-2-yl]hydrazino} 2,3 dihydrospiro [bite味和[2,3-g][l,4]本二乳地圜烯_8,3'_ρ引嗓]_2,(ι,η)_ ketone; (S)-l'-{[5 -(Trifluoromethyl)pyran-2-yl]hydrazide 2,3 dihydrospiro [bito-and-[2,3-g][l,4]-and-oxygen sulphate _8,3 '_P5| I»朵]_2, (ι,Η)-ketone; (S)-l'-(p-pyridin-2-ylindenyl)-2,3-dihydrospiro[吱,[2, 3_g][1,4]benzodioxan Benzene-8$吲哚]-2·(1Ή)-net; 1 -[3-(difluoromethyl)indolyl]-2,3-dihydrospiro[吱,[2,3-g] [i,4]benzodioxanthene-8J-啕哚]-2'(1Ή)-one; 5-[(2'-keto-2,3-dihydrospiro[吱喃和[2 ,3_g][1,4]benzodioxanthene_8 3,_峋哚]-Γ(2Ή)-yl)methyl] oleno-2-carboxylic acid methyl ester; Γ-pentyl-2 ,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxolene-8,3,_吲哚]-2'(ΓΗ)-one; (8R) -1'-[(2S)-1,4-dioxoindole-2-ylindenyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzoic Oxygen olefins _8,3,_w 哚]_2, (1, 印-ketone; 143924-SP-20091127-1 -54- 201020257 (8S)-14(2S)-1,4-dioxane 圜2_ylmethyl]_2,3_dihydrospiro[furo[2,3-g][l,4] benzodioxanthene_8,3,_吲哚]_21(1 ketone-ketone (8S)-r-[(2R)-l,4-Dioxaindole_2_ylmethyl]_2,3_dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene _8,3·_Ρ 嗓]_2.(1Ή)-ketone; Γ-[2-(2-methoxyethoxy)ethyl]_2,3_dihydrospiro[吱 并[2,3_g][14]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-鲷; 5-[(2'-keto-2,3- Dihydrospiro [2,3-g][l,4]benzodioxanthene-83- 吲哚Η'(2Ή)-yl) fluorenyl] benzoate·2_carboxylic acid; ® Ν,Ν·dimethyl base! [(2'-ketodihydrospiro[[,,,,,,,,,,,,, (8S)-r-{[3-(Trifluoromethyl oxaridinyl-2-yl)methyl b 2 3_dihydrospiro[吱,[2,3 -g][l,4]benzodioxanthene oxime]_2,(1Ή)-stuffed j; (8S)-l'-[(5-pyridylpyridin-2-yl)indenyl]_2 , 3-dihydrospiro [snolo[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one; 1'- (diphenylhydrazinyl)-7'-indolyl-2,3-dihydrospiro [bito-and-[2,3-g][i,4]benzodioxolene-8,3'-吲哚]-2'(1Ή)-ketone;

A 4-Xiyl-1'-(diphenylmethyl)-2,3-dihydrospiro[2,3-g][i,4]benzodioxene-8,3. ?丨哚]-2,(1Ή)-ketone; 41-bromo-indenyl-methyl-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene Alkene-8,3'-吲哚]-Τ(ΓΗ)-one; Γ-(diphenylfluorenyl)-4'-fluoro-2,3-dihydrospiro[吱,[2,3_g][ 1,4] benzodioxene terpene 哚]-2·(1Ή)-ketone; Γ-(4-fluorophenyl)-2,3-dihydrospiro[furan and dioxin _8,3'-吲哚]-2,(1Ή)-ketone; 143924-sp-20091127-1 •55· 201020257 1 -(monophenylmethyl)_4'_trendolin_3_yl_2 3_ Dihydrospiro[吱,[2,3 phantom (4) benzodioxanthene-8,3'-吲哚]-2,(1Ή)-one; 1-(monophenylmethyl)-4'- (4-phenoxyphenyl)_2,3-dihydrospiro[Ρ,[2,3_ε][1,4] stupid and dioxin, -8,3'-吲嗓]-2, (1Ή)-keto; 5-bromo-indenyl-(pyridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene Alkene-8,3,-吲哚]-2,(1Ή)-_ ; 2·-keto-1,-(pyridine_2_ylindenyl η,, 2,2,,3_tetrahydrospiro [ Bite and [2,3_g][i 4]benzoxoxyterpene-8,3'-θ|p]-5'-carbonitrile; 5-bromo-indenyl-(diphenylfluorenyl) _2,3_Dihydrospiropyrano[2,3_g][14]benzodioxanthene-8,3,-哚]-2'(ΓΗ)-ketone; 1 -(monophenylmethyl)_5'-mercapto-2,3_dihydrospiro[吱3[g]g[14]benzodioxanthene -8,3·-吲哚]-2'(1Ή)-ketone; Γ-methyl-2'-keto-l',2,2,,3-tetrazole bromo[2,3 -g][i,4]benzodioxanthene-8,3'-啕哚]-4·-phenyl decanoate; 4$dimethoxy·Γ_{[5-(^fluoromethyl) ) 吱 _2 _ _ _2 _2 _2 _2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 ,(1Ή)__ ; 477'-dimethoxy-indole-[2-(2-methoxyethoxy)ethyl]_2,3_dihydrospiro[吱,[2,3-g] [l,4]benzodioxanthene_8,3'_啕哚; 6-[2-(2-decyloxyethoxy)ethyl]_2,2',3,3'-four Hydrogen snail [1,4-dioxoisene[2,3-fH 嗓-8,8'-pyrano[2,3-g][l,4]benzodioxanthene]- 7(6Η)-keto 6'-(4-methoxybenzyl)-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene- 8,8'-[1,3> Retazo[5,4-eH 哚]-7,(6Ή)-one; 7'-Fluoro-2,3-dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene_8,3,-4丨哚]-2'(1Ή)-one; 143924-SP-20091127-1 -56- 201020257 4'-bromo -2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene-8,3,_4 哚]-2'(1Ή)-one; 4' -Fluoro- 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene??]-2'(1Ή)-one;奎 -3--3-yl-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene _8,3,_ 吲哚]-2' ( 1Ή)-ketone; 4'-(4-phenoxyphenyl)-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8, 3'-吲哚]-2'(1Ή)-ketone; ❹ 5'-mercapto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Terpene _8,3ι_ρ?| 哚]-2'(ΓΗ)-ketone; 2,3-dimer snail [吱,[2,3-g][l,4]benzodioxanthene-- 8,8'-[1,3>sodium sulphate [5,4-^4 丨嗓]-7'(6Ή)-one; 4,6'-didecyloxy-2,3-dihydrospiro[吱 并[2,3$][1,4]benzodioxanthene 浠-8J-吲哚]-2'(1Ή)-ketone; 3'-[2-(fluoro-fluorenyl)-yl ]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8, Γ-茚]-2'(3Ή)-one; 3- [(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3,-吲哚]-Γ( 2Ή)-yl) fluorenyl]benzonitrile; fluoro-3-methoxy -2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8J-吲哚]-2·(1Ή)-one; 4- [ (2'-keto-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3,- 吲哚]-Γ(2Ή) -yl)mercapto]benzonitrile; Γ-(4-isoxazol-5-ylbenzyl)-2,3-dihydrospiro[furo[2,3-g][l,4]benzo Dioxetene-8,3'-吲哚]-2'(1':«)-one; 143924-SP-20091127-1 -57- 201020257 1·-{[6-(trifluoromethyl) P is pyridine _3•yl] fluorenyl}_2 3_dihydrospiro [biting mers [2 3 g] [l 4] benzodioxanthene-8,3'-峋哚]-2, ( 1Ή)-ketone; 1 -[(5-acidylpyridin-2-yl)methyl]-2,3-dihydrospiro!> Furano[2,3-g][l,4]benzo Dioxogene-8,3'-吲哚]-2'(1Ή)-one; 14(3-fluoropyridin-2-yl)indenyl]-2,3-dihydrospiro[furan[ 2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1'11)-one; Γ-(pyridin-2-ylindenyl)- 4,-quinolin-3-yl-2,3-dihydrospiro[,,[2,3-g][l,4]benzodioxene-8,3'-吲哚]- 2,(1Ή)-keto; 4-(4-phenoxyphenyl)_1'-(pyridine-2-ylmethyl)_2,3_dihydrospiro[furo[2,3-g][l , 4] benzene Dioxane sulphate _8,3'-4 pulo]_2, (ι'η)-ketone; Γ-[(3,5-dioxacridin-2-yl)methyl]_2,3_2 Hydrogen snail [啥,[2,3_g][1,4]benzodioxanthene-8,3'-吲哚]-2·(ΓΗ)-one; 3-{[(8S)-2 '-S-Homo-2,3-dihydrospiro[吱,[2,3-g][;[,4]benzodioxene-8,3'-called 哚]-1' ( 2Ή)-yl]methyl} abbreviated nitrile; (8S)-r-[(5-fluoropyridin-2-yl)indolyl]-2,3-dihydrospiro[吱和dioxane Alkenyl-8,3'-吲哚]-2'(1Ή)-one; (8S)-r-[(3-fluoropyridin-2-yl)methyl]-2,3-dihydrospiro[吱喃[2,3_§][1,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; (S)-l-(2-ketobutyl) -3,7-dihydro-2-indole-spiro[benzofuro[5 6_b][1,4]dioxopinene-8,3'-dihydroanthracene-2,-one; -[(4-fluoropyridin-2-yl)indolyl]_2,3_dihydrospiro[c-buto[2,3 g][1,4]benzodioxene-8,3' -吲哚]-2'(1Ή)-ketone; 14(3-carbenylpyridin-2-yl)indolyl]-2,3-dihydrospiro[, succinyl[2 3 g][1,4] Benzodioxanthene-8J-吲哚]-2·(1Ή)-_ ; 143924-sp-20091127-1 -58- 201020257 Γ_[2_(Difluoromethyl)-yl]-2,3- Dihydrogen Snail [吱,[2,3-g][l,4]benzodioxanthene -8,3'-吲嗓]_2·(ι,η)_one; __1'-[2-( Trifluoroindolyl]-2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-巧哚]-2 , (1Ή)-ketone; 5·-methyl_1'-{[3-(trifluoromethyl)ρ-pyridyl-2-yl]methyl b 2,3 dihydrospiro [biting and argon [2, 3-苢][1,4] stupid and dioxane decene _8,3'_ 十朵]_2, (1, im-ketone; (8S)-r-[2-(trifluoromethyl) ]2,3_dihydrospiro[唉,[2,3 g][i,4]benzodioxanthene-8,3,-吲哚]-2·(1Ή)-one;

4'-Bromo-1,-(pyridylmethyl)_2,3_dihydrospiro[吱,[2,3_g][i,4]benzodioxanthene-8,3,-啕哚]-2,(1Ή)-ketone; 1 -(2,1,3-benzoxadiazole_5-ylindenyl)_2 3_dihydrospich-benzo-benzodioxanthene- 8,3,-吲哚]-2, (ΓΗ>ketone; 1 -(1,3-benzopyrimidin-2-ylmethyl)·2,3-dihydrospiro[ollenyl OgDA benzoate Oxadecene-8,3'-吲哚]-2,(1Ή)-one; Γ-[(1-methyl-1Η-benzimidazole_2-yl)indolyl]_2,3-dihydrogen Snail [furo[2'3-g][l,4]benzodioxolene _8,3'_吲哚]_2·(ΓΗ)·嗣; Γ-{[2-(1-A Ethyl ethyl hydrazine, 3_oxazole _4_yl] fluorenyl}_2,3_dihydrospiro [bito-and-[2,3-g][l,4]benzodioxene _8,3 '_吲嗓] is called gong; l'-(2,l,3-benzoindene 嗤5-ylindenyl)_2,3 dihydro snail [biting mers [2,3 liu,4]benzene And dioxerem-8,3'->·anthracene]-2,(1Ή)-one; 4-[(2,-keto-2,3_dihydrospiro[biting and argon [2] , 3_g] [1,4] stupid and dioxane decene _8,3 p 丨嗓 丨嗓] -1 '(2 Ή)-yl) fluorenyl] hexahydro p than bite _i acid-containing third butyl ester; lH2, um7-5-ylmethyl)_2,3 dihydrospirate [material and [2 3 scratch (10) Dioxetene-8,3'-吲哚]-2,(1Ή)-one; 143924-SP-20091127-1 -59- 201020257 1 -{[6-(di-Imethyl)p ratio bite_ 2_基]曱基}-2,3-一虱螺[pfu-[2,3-g][l,4] benzodioxene-8,3'-,?丨哚] -2'(1Ή)- Brewing 1 ; 1 {[2-(Difluoromethyl)ρ than biting _3_yl]methyl}-2,3-a snail [ρ夫鸣和[2,3- g][i,4] stupid and dioxane terpene 哚]-2'(1Ή)-ketone; 1 {[3-(二免曱基)ρ ratioρ井_2_基]曱基}-2 , 3-oxo snail [bite and [2,3-g][l,4] stupid and dioxerem-8,3'-吲哚]-2'(1Ή)-Ι同; 1 { [4-(di-I yl) ρ ratio bite _3_ yl] methyl}-2,3-digas sulphide 0 nan [2,3_g][i,4] benzodioxanthene -8,3'-key 哚]-2'(1Ή)-ketone; 1 [(6-a gas-based p-bito-2_yl)methyl]-2,3-two wind snail [puffalo[ 2,3_g][i,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; 1 -[(2-methoxybend _5_yl) Indenyl]_2,3_dihydrospiro[Uf-[2,3_g][i,4]benzodioxanthene-8,3'-throindole]-2'(1)-ketone ; 1 -[(6-decyloxyp to bite_3_yl)methyl]·2,3-dihydrospiro [biting benzo-dioxanthene-8,3·-吲哚]- 2'(1Ή)-ketone; (8SM' Specific tillage _2_ mercapto)_2,3_dihydro snail [biting and sulphonating [^~^ benzodioxanthene-8,3,-吲哚]-2,(1Ή)-one; 8S)-14(2-decyloxypyrimidin-5-yl)methyl]_2,3_dihydrospich-[2 3gKl,4] benzodioxanthene-8,3,-吲哚]-2,(1Ή)-ketone; *(8S)_1 'Bite-2_ylmethyl)-2,3_dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene-8,3,-啕哚]-2'(1Ή)-one; 4_sayyl-1'-{[3-(trifluoromethyl)pyridine-2-yl曱 }}_2,3-dihydrospiro[吱,[2,31][1,4]benzodioxanthene_8,3,-吲哚]_2, (1,11),; 1 _[(2,2-difluorocyclopropyl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8 ,3,-吲哚]-2'(1Ή)-ketone; 143924*sp-20091127-1 •60· 201020257 Γ-mercapto-2,3-dihydrospiro[吱,[2,3-g] [l,4]benzodioxanthene _8,3,_ 丨哚 丨哚]-2'(1Ή)-ketone; Γ-{[4-(trifluoromethylhydrazine, 3-, therazole- 2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-2' (1Ή)-ketone; (2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene _8,3,_啕哚]-Γ(2Ή)-yl)acetonitrile; 2-[(2-mercapto-2,3-diindole][N,N,[2,3-g][l,4]benzodiox圜 圜 吲哚]-1'(2Ή)-yl) fluorenyl>ethylpyridin-3-carboxylate; ® 1 ° quin-2-ylmethyl)-2,3-dihydrospiro[吱喃[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one; 1 -[(4,6-__甲甲Oxygenate bite-2-yl)methyl]-2,3-dihydrospiro[pf. Nanhe [2,3_g][i,4] benzodioxanthene-8,3·-嘀哚]-2·(1Ή)-one; (S)-l-pentyl-2,3- Dihydrospiro[吱β南和[2,3-g][l,4]benzodioxanthene·8,3'_啕哚]-2'(1Ή)-one; (R)-l -pentyl-2,3-one snail [吱,[2,3-g][l,4]benzodioxanthene _8,3,_ 丨哚]-2·(1Ή) -ketone; φ Γ-hexyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3,_ρ5| 哚]-2 丫ΓΗ)-ketone; 1-(2-cyclopropylethyl)-2,3-one snail [pf-pyrano[2,3-g][l,3]benzodioxanthene-8 , 3.哚]-Χ2Ή1Ή)-ketone; Γ-(2-ethoxyethyl)-2,3-dihydrospiro[吱,[2,3-g][l,3] stupid and dioxygen Alkenyl-8,3'-throindole]-2·(1Ή)-one; Γ-(4-methoxybutyl)-2,3-dihydrospiro[c-benzodioxanthene-- 8,3'-吲哚]-2'(1Ή)-ketone; • 61 - 143924-SP-20091127-1 201020257 1L(3_methoxypropyl)-2,3-dihydrospiro[吱[2,3-g][l,3]benzodiazepinee-8,3'-吲哚]_2,(1Ή)-one; 1-(3-nitrobenzyl)_2,3_ Dihydrospiro[吱,[2,3-g][l,3]benzodioxolene-8,3'-吲哚]_2, (ι,Η)-ketone; 1*-pyrazol-5-ylmethyl)-2,3-dihydrospiro[sn-[2,3-g][l,3]benzodioxanthene-8,3,-啕哚]-2'(1Ή)-ketone; 1'-{[5-(trifluoromethyl]>pyridinyl-2-yl]methyl丨_2,3_dihydrospiro [味喃和阳幻即] Benzodioxanthene-8,3,-吲哚]-2·(1Ή)- Brewing I; 1 -{[3-(Difluoromethyl)ρ~唆_2_yl]methyl b 2 ,3-dihydrospiro[吱,[2,3-g][i,3] benzodioxanthene-8,3'-啕哚]-2,(1Ή)-one; Γ-[ (3-pyridin-3-ylisoxazole-5-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-phan [1,3] benzodiazepine Oxadecene-8,3·-,5丨哚]-2'(1Ή)-one; (8R)-l'-{[3-(trifluoromethylcyclopyridine-2-yl)methyl) -2,3-dihydrospiro[吱,[2,3-g][l,3]benzodioxene _8,3'-吲哚]-2'(1':")- Ketone; N,N-dimethyl-3-[(2'-keto-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene -8,3'-(5)哚]-1,-(2Ή)-yl)indolyl]benzenesulfonamide;norfosin-4-mercaptopurine]2,3-diindole[吱π南和[2,3-g][i,4]benzodioxanthene-8,3'-thoracic]-2'(1Ή)-one; 14(4-mercapto-1,2 ,5-oxadiazol-3-yl)indenyl]_2,3_dihydrospiro[furo[2,3_g] [1,4]benzodioxene _8,3'-p 哚]_2'(l,H)-one; 2,3-difluorobenzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Terpene-8,3'-吲哚]-2'(1Ή)-one; Γ-(3,5-difluorobenzyl)-2,3-dihydrospiro[吱,[2,3-g ][l,4]benzodioxanthene-8,3'-throindole-7(1)-one; 143924-sp-20091127-1 -62· 201020257 Γ-(4-fluorobenzyl -2,3-dihydrospiro[吱,[,2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one ; 1·-(2-gasyl-4-fluoro -2,3-dihydrospiro[吱-benzodioxanthene-8,3'-峋哚]-2'(1Ή)-one; Γ-[(1-methyl-1Η- Benzotriazol-5-yl)methyl]_2,3_dihydrospiro[Nitrate [2 3 g] [1,4] benzodioxanthene -8,3'-吲嗓]_2 , (1Ή)-ketone; 1-[(3-difluoromethoxyXyl]-2,3-dihydrospiro[吱,[2,3_g][i,4]benzodioxanthene -8,3'-吲哚]-2'(1Ή)-ketone; 〇1 _[(2_fluoroyl_6_difluoromethyl) aryl]_2'3_dihydrospiro[吱喃和[ 2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-2·(1Ή)-one; 1 -[(2-fluoro-5-difluoromethyl) Base)]-2,3-dihydrospiro[,,[2,34(^4]benzodioxolene-8,3'-吲哚]-2'(1'11)- Ketone; Γ-[(2-difluoromethoxy)carbonyl]_2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8, 3M丨哚]ΚΓΗ)-ketone; Γ-[2-(2,2,5-tridecyl-1,3-dioxoland-2_yl)ethyl]_2,3_dihydrospiro[吱并和馨[2'3_§][1,4]benzodioxanthene-8,3'-吲嗓]-2,(1,11)-one; 7'-fluoro-anthracene ( Pyridin-2-ylmethyl)-3,7-dihydro-2-indole-spiro[benzofuro[5,6-b][l,4]dioxolysene_8,3,·dihydroindole Bu ],_2,_嗣; 7·-fluoro-indole-((3-(trifluoromethyl)p-pyridyl-2-yl)indolyl)_3,7-dihydro-2H-spiro[benzofuran And [5,6-b][l,4]dioxolene-8,3,-dihydroanthracene-2,-one; 3'-[2-(di-halofluorenyl)] -2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8, Γ-茚]-2'(3Ή)-one; 1'- [(5-1-Acridine-3-yl)indolyl]-2,3-dihydrospich-[2,34][1,4] benzodioxanthene-8,3' -啕哚]-2,(1Ή)-ketone; 143924-SP-20091127-1 •63- 201020257 (8S)-l'-[(5-fluoropyridin-3-yl)methyl]_2,3- Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3·-吲嗓]-2·(1Ή)-net; Γ-[4-(芊Oxy))hanyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3W, dub]-2'(1Ή) -ketone; (8S)-r-[4-(yloxy)-yl]-2,3-dihydrospiropyrano[2,3-g][l,4]benzodioxanthene卜朵]_2'(1Ή)-嗣; {5-[(2'-steel-based-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxan) Terpene·8,3ι_ 令]-Γ(2Ή)-yl) fluorenyl]acridine_2_yl}amino carboxylic acid tert-butyl ester; Γ-[3-(yanooxy)propyl]- 2,3- Dihydrospiro[N-[2,3-g][l,4]benzodioxene-8J-啕哚]-2\1Ή)-silk; (2-keto-2,3- Monohydrospiro[吱啥,[2,3-§][1,4]benzodioxolene _8,3,_啕哚]-Γ(2Ή)-yl)ethyl acetate; r-{ [(4S)-2,2-dimethyl-1,3-dioxoindolyl] fluorenyl}_2 3 dihydrospiro[snolo[2,3-g][l,4]benzo Dioxetemene _8,3,y pulo]_2,(1Ή)ketone; 4·-bromo-indolyl-pentyl-2,3-dihydrospiro[吱,[2,3_g][1 , 4] benzodioxanthene-8, 3% 5 丨哚]-2Χ1Ή)-one; 3- [(2'-keto-2,3-dihydrospiro [biting mers [2,3_g] ][1,4]benzodioxanthene_8,3,_峋哚]-1'(2Ή)-yl)methyl]benzoic acid oxime ester; 4-[(Τ-keto-2 , 3-dihydrospiro[吱 并 dioxodioxene _8,3,_ 嘀哚]-1·(2Ή)-yl)methyl]benzoic acid oxime ester; 14(4-mercapto? Fulin-2-yl)methyl]_2,3_dihydrospiro[c-buto[2 3 g][i 4]benzodioxanthene-8,3·-吲嗓]-2,( 1Ή)-ketone; (8S)-l'-{[(2S)-4-benzylmorpholine·2_yl]methyl}·2 3 dihydrospiro [bito-[2,3-g] [l,4] stupid and oxy-terpinene _8,3ί 嗓]_2, (ι,η) ketone; 143924-SP-20091127-1 201020257 4-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene_8,3,_ 哚 哚]- Γ(2Ή)-yl) fluorenyl] benzoic acid ethyl ester; 2-[3-(2'-keto-2,3-dioxaspiro[吱,[2,3-g][l,4 Benzodioxanthene _8,3,_ p 丨嗓 丨嗓]-Γ(2Ή)-yl)propyl]-1H-iso-p?-d-l,3(2H)-dione; 2 -[3-(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene_8,3,_p bow ]]-1'(2Ή)-yl)propyl]-1H-iso-β-do-1,3(2H)-diindole; (88)-1-[2-(2-曱-lactylethoxy) ) ethyl]-2,3-dihydrospiro [flavor. Nanhe [2,3_@][1,4] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; ® 6-[2-(2_曱oxy Ethoxy)ethyl]_2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene -8,8'-[1,3> [5,4-e] noisy]-7,(6Ή)-ketone; 6'-(pyridin-2-ylmethyl)-2,3-dihydrospiro[furo[2,3-g][ i,4]benzodioxanthene-8,8·-[1,3>- oxazolo[5,4-e]吲哚-7,(6Ή)-嗣; 4',6'- Dimethoxy-1'-[2-(2-decyloxyethoxy)ethyl]_2,3_dihydrospiro[snolo[2,3-§][1,4]benzoic Oxygen-ene-ene-8,3'-4b]-2'(1,11)-steel; 4'6-dimethoxy-1'-(pyridin-2-ylmethyl)-2,3 - dihydrospiro[furo[2,3-2][1,4] benzodiazepine-8,3W丨哚]-2·(1Ή)-one; (2·-keto- 2,3-Dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3,_吲哚]-Γ(2Ή)-yl)acetic acid; 1' -Methyl-2'-keto-oxime, 2,2',3-tetrahydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene-8,3' -吲哚]-4'-carboxylic acid; 3-[(3-aminopyridin-2-yl)indenyl]-2,3-dihydrospiro [bite. Nanhe [2,3-g][l,4]benzodioxanthene-8,1'-茚]-2'(3Ή)-one; 3'-{[3-(methylsulfonyl) Cycloazin-2-yl]methyl}_2,3_dihydrospiro [biting and cation] benzodioxanthene-8,1,-茚]-2,(3Ή)-one; 65- 彳71.\ 143924-sp-2〇〇91i27-l 201020257 2- [(2·-keto-2,2\3,3'-tetrahydrospiro[吱嗔,[2,3-g]] [l,4]benzoxanthene-8, Γ-印]-3'-yl)methyl]p is more than a bite of a bet; (8S)-l'-{[3-(two Fluoromethyl)pyridine·2-yl]methyl}-2,3-dihydrospiro[吱,[2,3$][1,4]benzodioxanthene_8,3|-啕哚]-2'(1'1!)-_; Ν,-hydroxy-3-[(2,-keto-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene-8,3'-峋哚]-1'(2Ή)-yl) fluorenyl] benzocarboximine amide; Γ-[3-(5-methyl-1 , 2,4-oxadiazol-3-yl)benzyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxene _8,3 '_峋哚]_2·(ι'η)-ketone; Γ-[4-(5-methyl-1,2,4-oxadiazol!yl)benzyl]-2,3-dihydrospiro[ Furando[2,3-g][l,4]benzodioxanthene_8,3'-吲哚]-2·(1Ή)-one; 3-[(2'-keto-2 , 3-dihydrospiro [cough and [2,3-g] [l,4]benzodioxanthene_8,3,_峋哚]-1·(2Ή)-yl)mercapto]benzoic acid; 4-[(2'-keto-2,3 - dihydrospiro [snolo[2,3_g][1,4]benzodioxolene_8,3,_吲哚]-Γ(2Ή)-yl)methyl]benzoic acid; -hydroxy-2-(2'-keto-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene-8,3'-吲哚-1 '(2Ή)-yl) acetamimidamine; Γ-{[5-(trifluoromethyl)-1,2,4-oxadiazole-3-yl]methyl}-2, 3-dihydrospiro[, succinyl[2,3-g][l,4]benzodioxanthene _8,3,_ΡΡ丨嗓]_2,(1Ή)_one; 2-(2 '-keto-2,3-dihydrospiro[pufrano[2,3-g][l,4]benzodioxene _8,3,_吲哚]-1' (2Ή )-yl)acetamidine; 1'-{[5-(trimethylsulfonyl)-1,3,4-oxadiazol-2-yl]methyl}-2,3-dihydrospiro Nanhe [2,3-g][l,4]benzodioxanthene_8 3,,哚]_2, (ι'η)-ketone; l'-(3-aminothiol) -2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxolene-8,3%?1 mouth] ketone; 143924-SP-20091127-1 •66 - 201020257 N-{3-[(2'-keto-2,3-diindole |> Furano[2,3-g][l,4]benzodioxanthene-8, 3 '-啕哚]-1'(2Ή)-yl)methyl]phenyl}methanesulfonamide; Γ-[(1-oxypyridin-2-yl)methyl]-2,3-dihydrospiro[吱 并[2,3-g][l,4]benzodioxanthene-8,3·-峋哚]-2·(1Ή)-one; 2-[(2'-keto- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene.ene_8,3,-吲哚]-1'(2Ή)-yl) A风 啶 -3--3-carboxylic acid; l'-[(3-amino ρ 咬 -2- -2-yl) fluorenyl]-2,3-dihydro snail [bit sulphur [2,3-g] [l , 4] benzodioxene decene-8,3·- 哚 哚]-2·(1Ή)-嗣 hydrobromide; ® Ν-{2-[(2'-fluorenyl-2,3_ Dihydrospiro[2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-Γ(2Ή)-yl)methyl]p-pyridyl Methanesulfonamide; Γ-(hexahydropyridin-4-ylmethyl)-2,3-dihydrospiro[c-butyl[2,3-g][l,4]benzodioxanthine Rare -8,3'-〃5 卜多]-2'(1Ή)-hydrazine hydrochloride; Γ-{[1-(1-methylethyl)hexahydropyridin-4-yl]methyl}· 2,3_Dihydrospiro[furo[2,3-g][l,4] benzodioxanthene _8,3'_丐丨嗓]_2, (rH)-keto hydrochloride; 1-[(1-mercaptohexahydropyridin-4-yl)indolyl]-2,3-dihydrospiro[N,[2,3_g][1,4] awkward and dioxane Alkene-8,3'-M丨嗓]-2'(1Ή)-hydrazine hydrochloride; 1 -(morpholine-2-ylmethyl)_2,3_dihydrospiro[吱,[2, 3 phantom, 4] benzodioxanthene-8,3'-吲哚]-2, (1Ή)-one; 1-{[4-(1_methylethyl)norfos-2 Methyl]dihydrospiro[N-[2,3-g][l,4]benzodioxanthene _8,3,_decaone (tetra) ketone; Γ-[(4-fluorenyl)福福淋_2_基)曱基]_2,3_Dihydrospiro [Cough π Nanhe sand phantom (10) benzodioxanthene-8,3'-吲哚]-2, (1Ή)-_ (8S>14(2S)-isofolin-2-ylmethyl]_2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanene-83 , -M noise>-2'(1Ή)- Brewing 1; 143924-sp-2009ll27-l •67- 201020257 (8S)-r-{[(2S)-4-Methylmorpholine_2_yl ]methyl b 23_dihydrospich-p-P,3-g][l,4]benzodioxanthene]one; 1'-{[5-(di-methyl)anthracene喃-2-yl]methyl}_2,3-dihydrospich-[2,3-g][i,4] benzodioxanthene -8,3Wbdu]-2·( 1Ή)-_ ; 4-[(2-keto-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxene _8,3'_吲哚]-Γ(2'Η)-yl) fluorenyl]phenylamine; 3-[(2'-keto-2,3-dihydrospiro[吱,[2, 3-g][i,4]benzodioxanthene_8,3,_嗍哚]-Γ(2Ή)-yl)indolyl]benzamine; Ν,Ν-dimercapto-3 -[(2'-keto-2,3-dihydrospiro[吱,[2,3_g][i,4]benzodioxanthene-8,3'-吲哚]-1·( 2Ή)-yl)methyl]phenylhydrazine; Ν-mercapto-2-[(2·-keto-2'3-dihydrospiro[吱,[2,3_g][1,4]benzene And dioxanedecene-8,3'-吲哚]-1'(2Ή)-yl)methyl>Carboxylamidine; Ν-(2-aminoethyl)-2-[(2'-keto-2,3-dihydrospiro[indenyl]OgKM]benzodioxene-8,34哚-1'(2Ή)-yl) fluorenyl carbarylamine dihydrochloride; Ν-(2-fluorophenyl)-4-[(2'-keto-2,3-dihydrospiro) [吱喃和[2,3_幻[14]Benzene bismuthene-8,3'-吲哚]-Γ(2Ή)-yl) fluorenyl]benzamine; Ν-(2- Fluorophenyl)-2-(2'-keto-2,3-dihydrospiro[furo[2 3_g](1)4]benzodioxanthene-8,3'-吲哚]-Γ(2Ή Ethylamine; Γ-mercapto-4'-(2-keto-2-indole-7-yl)-2,3-dihydrospiro[吱,[2,3-g] [i,4]benzodioxanthene-8,3'-啕哚]-2\1Ή)-one; Γ-mercapto-4'-(2-ketotetrahydrop to 4 -l- -2,3-dihydrospiro[?,[2,3-g][l,4] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one Γ-mercapto-4'-moffolin-4-yl-2,3-dihydrospiro[吱,[2,3_g][i,4]benzodioxane 143924-sp-20091127-1 68 · 201020257 cedarene-8,3'-啕哚]-2·(1Ή)-one; 1'-methyl oxa (2-ketopyridine-l(2H)-yl)-2,3-dihydro Snail [吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲嗓]-2,(1Ή)-one; 4'- -1'-methyl-2,3-dihydrospiro[,,[2,3_g][1,4]benzodioxanthene-8,3'-吲哚]-2'(ΓΗ )-ketone; N-(l'-methyl-2'-fluorenyl-l',2,2',3-tetrahydrospiro[吱,[2,3_g][1,4]benzodioxole Cyclodecene-8,3'-θ丨嗓]-4'-yl)cyclobutanol carboxamide; Ν-(1·-mercapto-2·-mercapto-l',2,2',3 -tetrahydrospiro-I; indolo[2,3_g][1,4]benzodioxolene-8,3'-tetrado]_4'-yl)-2-(trifluoromethyl)benzene Indoleamine; N-(l'-mercapto-2'-keto-1',2,2',3-tetrahydrospiro[吱,[2,3_g][1,4]benzodiox圜 圜 -8,3'-〇5丨嗓]-4'-yl)f calcination guanamine; Ν-(Γ-曱- 2'-keto-oxime, 2,2', 3-four Hydrogen snail [biting and argon [2,3_g][1,4]benzodioxanthene -8,3^5 pulo]-4'-yl)cyclohexene sulphonate; Ν-(Γ- Methyl-2'-keto-oxime, 2,2',3-tetrahydrospiro[吱3[g]g[14]benzodioxolene-8,3 W丨哚]-4' -yl)cyclopentane carboxamide; Ν-(Γ-曱-yl-2', Γ-Γ, 2,2',3-tetrahydrospirobi-[2,3_g][1,4]benzene And dioxane terpene-8X嗓]-4'-yl)acetamide; N-(l'-methyl-2'-keto- , 2,2',3-tetrahydrospirobin [2,3_g][14]benzodioxanthene -8,3^5丨嗓]-4'-yl) cyclopropanone slow Amine·, N-(l'-methyl-2'-keto-iso-tetrahydrospirobin-yang-na (4) benzodioxanthene -8,3*-p?丨嗓] Benzoylamine; 2-methoxy-indole-(Γ-methyl-2·-_yl-l,,2,2,,3-tetrahydrospiro[吱,[2,3-g ][i,4]benzoxa-oxygen sulphate 丨p朵]-4'-yl)ethinamine; N-(l'-mercapto-2'-keto-l',2'2' ,3-tetrahydrospiro[c-buto[2,3_g][1,4]benzodioxan 143924 Today 20091127-1 -69· 201020257 Terpene-8,3'-吲哚]-4'-yl Acetamide; Ν-(Γ-methyl-2'-keto-1,2,2,3-trihydrospiro[,,[2,3-g][l,4]benzo Dioxoenene-8,3'-W哚]-4,-yl)pentaamine; 2,2-dimercapto-indole-(1·-methyl-2·-keto-anthracene, 2 , 2',3-tetrahydrospiro[,,[2,3-g][l,4] benzodioxanthene-8,3'-啕哚]-4'-yl)propanamide Ν-(Γ-曱-yl-2'-keto-l',2,2',3-tetrahydrospiro[吱,[2,3-g][l,4] stupid and dioxin Alkene-8,3'-i丨哚]-4,-yl)hexylamine; Ν-(Γ-曱-yl-2'--yl- , 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8,3·-吲哚]-4·-yl)g Indoleamine; 2-(2-decyloxyethoxy)-indole-(1,-methyl-2,-keto-1,2,2,3-trihydrospiro[吱?[2 ,3-g][l'4]benzodioxanthene-8,3'-called 丨嗓]-4'-yl)acetamide; 1-hexyl-3-(anthracene-yl-2 '-keto-anthracene, 2,2',3-tetrahydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene-8,3'-thirsty]- 4'-yl)urea; 1-cyclopentyl-3-(indole-indolyl-2'-keto-oxime, 2,2',3-tetrahydrospiro[pf-fol[2,3-g ][i,4]benzodioxanthene-8,3'-吲哚]-4'-yl) vein; 1-cyclohexyl-3-(anthracene-methyl-21-keto-anthracene, 2,2',3-tetrahydrospiro[吱,[2,3_g][1,4]benzodioxanthene-8,3'-蚓哚]-4'-yl)pen I; N -cyclohexyl-fluorenyl-methyl-2'-keto-indole, 2,2',3-tetrahydrospiro[p-benzodioxanthene-8,3*-呻哚]-4' - Carboxylamidine; Ν-cyclopentyl-fluorenyl-mercapto-2'-keto-1',2,2·,3-tetrahydrospiro[唉,[2,3_g][i,4]benzene Dioxodecene-8,3'-,5丨哚]-4'-carboxamide; N-cyclopropyl-fluorenyl-fluorenyl-2'-keto-l',2,2', 3-tetrahydrospiro[吱Chew and [2,3_g][i,4]benzodioxanthene-8,3'-吲哚]-4·-carboxamide; 1'-mercapto-4'-(tetrahydropyrrole- 1-ylcarbonyl)-2,3-dihydrospiro [bite and drink [2,3^1^4] stupid 143924-sp-20091127-1 -70- 201020257 and dioxanedecene-8,3·-吲哚]-2·(1Ή)-ketone; Ν-(2-methoxyethyl)_r_methyl_2, keto-yl, 2, 2,, 3, hydrogen snail 2,3-g][l,4]benzodioxanthene _8,3'_吲嗓]_4,- slow-acting amine; N-(4-fluorohanyl M, _f base·2 ketone Γ·Γ, 2, 2,, 3π Hydrazino[(10)][14] benzodioxanthene-8,3'-吲嗓>4'- slow-acting amine; Ν-hexyl-1,- Methyl-2'-keto 4,2,2,,3-tetrahydrospiro[吱,[2,3_g][1,4]benzodioxanthene-8,3'-thirsty -4,-Carboxylamidine; Γ-fluorenyl-2·-keto-N-(acridin-2-ylindenyl H,, 2,2,,3,hydrospiro[2, 3-g][l,4]benzodioxanthene _8,3,_吲哚]_41 醢 醢 amine; N-(4-fluorophenyl H·-methyl 2, keto _ Γ, 2, 2 Ι, 3_ tetrahydro snail [bite suffix [2,3 g][i,4] benzo-oxygen sulphate -8,3'-M budto]-4'- valine amide ; 4'-Amino-indole-pentyl-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxan Terpene-8,3'-啕嗓]-2'(1Ή)-one; 4·-(benzylamino)-Γ-{[3-(trifluoromethylcyclopyridine·2·yl)methyl b 2,3_Dihydrospiro[吱0南和[2,3-g][l,4]benzodioxanthene-8,3,-β 哚]-2,(1Ή)-one; 4 '-Amino-indole-{[3-(trifluoromethylcyclopyridine-2-yl)methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene _8, ♦ ] _2 · (ι·η)-ketone; 4'-hydroxy-2,3-dihydro snail [c- s[2,3-g][l,4 Benzodioxanthene _8,3,_蚓哚]-2Χ1Ή)-one; 4·-hydroxy-1'-methyl-2,3-dihydrospiro[吱,[2,3- g][l,4]benzodioxanthene-8,3'-β 哚]-2,(1Ή)-one; Γ-mercapto-4'-indole 吱-2-yloxy) _2,3_Dihydrospiro [Blowing and [2,3-g][l,4]benzodioxanthene -8,3'-吲嗓]-2·(1Ή)-_ 4-[ 2-(2-decyloxyethoxy)ethoxy]_ι'-methyl-2,3-dihydrospiro[ρ夫η南和143924-sp-20091127-1 -71 - 201020257 [2,3 -g][l,4]benzodioxanthene_8 3,_吲哚]_2,(1Ή)one; 1-mercapto-4-{[3-(trifluoromethyl)pyridine_2 · ]]oxy} 2 3 dihydrospiro [furan [^^(4)(1)^benzodioxanthene^^吲哚^^-ketone; 1'-mercapto-4'-[4-( Fluoromethyl)phenoxy]2 3_dihydrospiro[吱β南和ο.〆] Stupid and diterpene tertene _8,3,_吲哚]_2, (ι,η) ketone; 4Η卞oxy)-1'-methyl-2,3_dihydrospiro[, succinyl[2 3_g][1,4]benzodioxolene _8,3'-吲哚]-2' (1Ή)-_ ; 1'-Methyl-4'-{[3-(Trifluoromethyl Cyclohexane) methoxy}_2,3_Dihydrospiro [Bite and [2,3-g] [l,4]benzodioxanthene·8,3,_ρ5丨哚]_2,(1Ή)__ ; φ 4′-(6-(diguanidino)pyridinyl)_1L (pyrobitone _ 2 曱 ))) 3,7 二气_2η· snail [benzopyrano[5,6-b][l,4]dioxene _8,3,_dihydroindole]_2, _嗣; 4X4-methoxyphenyl Η '-(pyridine_2_ylindenyl)_3,7-dihydro-211_spiro[benzofuro[5,6-b][l,4]dioxene Rare -8,3'-dihydroindole]_2, ketone; 1'-mercapto-441H-pyrazol-3-yl)-2,3-dihydrospiro[吱,[2,3- g][l,4] stupid and dioxerem-8,3'-thirsty]-2\1Ή)-_ ; 4'-furan-3-yl-indole-methyl-2,3-di Hydrogen snail [[,,,,,,,,,,,,, ,-(1Η-pyrazol-4-yl)-2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one; 1'-methyl-4'-(1-methyl-1H-H4-yl)·2,3 - dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8,3'-啕哚]-2'(γη)-_ ; Γ-fluorenyl- 2'-keto-anthracene, 2,2',3-tetrahydron snail [bite-and-[2,3_g][1,4]benzodioxanthene-8,3'-thirsty]-4 '-carbonitrile; 1'-mercapto-2'-keto-1',2,2·,3-tetrahydrospiro[吱,[2,3_g][1,4]benzodioxanthene 143924-sp-20091127-1 - 72 - (S) 201020257 ene-8,3'-吲嗓]_4'_retinamide; 1-methyl_4'-(5-methyl-12,4_p No.2 Oxazolyl) 2,3 dihydrospiro[furo[2,3-g][l,4]benzodioxanthene_8,3,♦, ketone; heart (3,5_ Dimercaptoisoxazole ketone Η '-mercapto-2,3-dihydrospiro [bito-and-[2,3-g] [1,4] benzodioxanthene _8,3i 4哚]_2,(ιή) ketone; N,1 -monomethyl-2'-keto-anthracene, 2,2,,3-indole hydrogen snail [吱,[2,3_2][1,4]benzo Dioxoenene-8,3'-μ丨哚]-4·-haloxime; Ν-cyclobutyl-1 -fluorenyl 2'-keto-oxime, 2,2,,3π snail矢 喃 benzodioxanthene-8,3,-吲哚]-4,-carboxamide; Ν, , Γ-dimethyl 2'__yl- to (10) tetrahydrospiro sulphate and cation is benzodioxanthene -8,3'- 嗓 嗓]-4'- slow oxime; 4 '-(3-曱Phenoxyphenoxy)_Γ_曱yl_2,3_dihydrospiro[N,3 g][1,4]benzodioxanthene-8,3 ,-吲嗓]_2,(ΓΗ)-ketone; Γ-methyl-4-phenoxy-2,3_dihydrospiro[furo[2,3_g][14]benzodioxanthene- 8J-吲哚]_2, (1,H)-ketone; 1·-methyl_4'-(3-isofan, linyl-4-ylphenoxy)_2,3_dihydrospiro [2 3_g][14] benzodioxanthene-8,3,-吲哚]-2'(1Ή)-one; 44(6-methoxyacridine! ))oxy]Γ_methyl_2,3_dihydrospiro[吱3[3,3]][1,4]benzodioxolene-8,3'-state 哚]-2, (1Ή)-ketone; 4'-(1'3-benzodioxantheneoxy)},indolyl-2,3_dihydrospiro[吱'[2'3-g] [l,4]benzodioxanthene _8,3,_啕哚]_2, (i'h)-ketone; 4H4-decyloxyphenoxy)_Γ_曱yl_2 3 dihydrospiro [吱吱[2 3_g][14]benzodioxanthene-8,3'-吲哚]-2,(1Ή)-one; V-methyl-4-decapyridyloxy) · 2,3_Dihydrospiro[吱,p,p,3-g][l,4]benzo 143924-sp-20091127-1 •73- 201020257 Dioxetene-8,3'-啕哚] -2·(1 Ή)-ketone; Γ-mercapto-4-(4-fluorobenzyloxy)-2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; 4'-(4-fluorophenoxy)-indole-indenyl 2,3-dihydrospiro失 并 [2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-2'(1Ή)-one; Γ-(4-benzyl) -2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxene-8J-吲哚]-Τ(ΓΗ)-one; Γ-(3- Hydroxypropyl)-2,3-dihydrospiro[furo[2,3-g][i,4]benzodioxanthene-8,3'-吲]-2'(1Ή)-ketone; _ 2-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene _8,3 '_吲哚]-Γ(2Ή)-carboxylate; 2-keto-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene Dilute _8,3,_吲哚]-Γ(2Ή)-sodium butyl-butyrate; l-{[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-ra 曱Tetrahydro-3aH-bis[1,3]dioxos(4'5-b:4',5'-d]pyran-5-yl]indolyl 2,3-dihydrospiro [味喃[2,3-g][l,4]benzodioxanthene_8,3ι_ρ 哚]_2,(ΓΗ)__; 6-deoxy-6-(T-keto- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene® ene-8,3'-啕哚]-Γ(2,Η)-yl) -D-galactose melanose; Γ-cyclopropyl-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxolene-8,3,啕哚]-2'(1Ή)-ketone; 1'-acetamido-2,3-dihydrospiro[,4,3_g][1,4]benzodioxene _8,3, _啕哚]-2Χ1Ή)-ketone; Γ-{[4-(trifluoromethyl)acridin-2-yl]indolyl}-2,3-dihydrospiro Alkene-8,3·-吲哚]-2,(1Ή)-one; -74- 143924-sp-20091127-1

(SJ 201020257 4-ethylidene _ι·_methyl_2,3_dihydrospiro[吱,[2,3 g][1(4)benzodioxan -8,3'-θ丨嗓]-2'(ΓΗ)-胴; Γ-methyl-4,-(2-methyl-1,3-thiazolyl)_2,3_dihydrospiro[吱][ng]^, 4] Benzodioxanthene dilute _8,3'_4 dumb]-2·(1Ή)-ketone; 4 (2-aminoserazole _4_yl)_Γ_methyl_2,3 dihydrospiro[cough喃[ng]^,4]benzodioxanthene-8,3,-吲哚]-2,(1Ή)-one; 4 (5hydroxy-indole-pyrazole-3-yl)-1 '-Methyl-2,3_dihydrospiro[Nitrate[2 3$]^(4) benzodioxanthene-8,3,-啕哚]-2'(1Ή)-one; φ 1 _[3_(3·methyl_1,2,4·"号二嗤-5-yl) 贵基]-2,3-dihydrospich and [2,3_g] [Μ]benzo Dioxetene _8,3,_啕哚]_2,(1Ή)__ ; 144-(3-amino-1Η-pyrazole-5-yl) aryl]_2 3_dihydrospiro And [2,3 g][l,4] benzodioxanthene-8,3,-啕哚]-2,(1Ή)-keto hydrochloride; 144-(3-methylΆ4-啐Diazole _5_yl)benzyl]_23_dihydrospiro[furo[2,3-g][l,4]benzodioxolene_8,3,_吲哚]_2, (1Ή )__ ; 2|-_yl-1'-(pyridyl-methylenemethyl)_1,,2,2,,3_tetrahydrospiro[11 Fusino[2,3_phantom [1,4]benzodioxanthene-8,3,-W哚]-5,-carboxyguanamine; Γ-[(6-morpholin-4- Pyridyl) fluorenyl]-2,3-dihydrospiro[c-buto[2,3-g][l,4] benzodioxanthene-8,3W丨哚]-2, ( 1Ή)-ketone; 14[6-(dimethylaminoidinyl)methyl b 2,3-dihydrospiro[吱,[2,3_g][1,4] benzodioxene -8,3,-啕哚]-2,(1Ή)-ketone; 1'-{[6-(dimethylaminothiaridin-2-yl)methyl}_2,3_dihydrospiro[吱And [2 3_g][14] benzodioxanthene-8,3,-W哚]-2,(1Ή)-one; 14{6-[(diphenylmethylene)amino]ρ ratio Pyridin-2-yl}methyl)_2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxolene_8,3'_啕哚]-2 '(1Ή)-_ ; 143924-sp-20091127-1 -75- 201020257 Γ-[(5-morpholine-4-ylpyridin-2-yl)indolyl]-2,3-dihydrospiro喃[2,3-g][l,4] benzodioxanthene-8,3·-峋哚]-2·(1Ή)-one; 1'-{[5-(diamine ))pyridinyl-2-yl]methyl}-2,3-dihydrospiro[ sniffing]Nan[2,3-g][l,4] benzodioxanthene-8,3, -啕哚]-2,(1,11)-鲖; 1·-[(6-aminop-pyridin-2-yl)methyl]-2,3-dihydrospiro [biting and [2, 3-g] [l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one; Bu [(6-keto-1,6-dihydropyridin-3-yl)曱基]_2,3_Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene,8,3'-ρ嗓]_2,(γη)-ketone ; 1 -[〇hydroxyl-pyridin-5-yl)indenyl]_2,3-dihydrospiro[吱α南和[2,3-g][i,4]benzodioxanthene-8, 3·-吲哚]-2·(1Ή)-ketone; Γ-[(1-mercapto-6-keto-l,6-dihydropyridin-3-yl)methyl]_2,3-dihydrogen Snail [bite and [2,3-g][l,4] stupid and dioxygenate _8,3,-ρ 嗓]_2, (ι,η)-ketone; Γ-[(6- Aminopyridin-3-yl)methyl]_2,3·dihydrospiro[唉,[2,3 g][1,4]benzodioxanthene-8,3·-吲哚]- 2·(1Ή)-ketone; Ν'-hydroxy-N-{5-[(2i-fluorenyl-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxole Terpene _8,3'-吲哚Η, (2Ή)-yl)methyl]pyridine_2_yl} quinone imine amide; Γ-([1,2,4]triazolo[ ^a]pyridine _6_ylmethyl)_2,3 dihydrospiro [bito-and-[2,3_phantom [1,4]benzodioxanthene _8,3'-吲嗓]_2' (i,h)-嗣; 14(2S)-2,3-dihydroxypropyl]-2,3-dihydrospiro[唉,[2,3_g][1,4]benzodioxanthine -8,3'-吲哚]-2'(1'11)-one; 6-[(2'-keto-2,3-dihydrospiro[indolylbenzodioxene_8 , 3, _ Θ 朵 ] Γ Γ Γ Γ Γ Γ Γ Γ Γ 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 比 或 或 或 或 或 或 或 或 或 或[2,3·8][1,4] stupid and dioxererene_8 3,- 143924-sp-20091127-1 -76- 201020257 啕哚]-Γ(2Ή)-yl) 曱基]峨Pyridine-2-carboxyguanamine. In this particular embodiment, 'another specific embodiment is a compound of formula (I) wherein -CH-, and oxime is -0-. In this particular embodiment, a specific embodiment is a compound of formula 1 which is 1'-[(211)-tetrahydrofuran-2-ylindenyl]-4H-spiro[吱,[3,2_g] [1,3] benzodioxanthene-6,3'-吲哚]-2·(1Ή)-one. In this particular embodiment, another embodiment is a compound of formula (I) wherein each of the formulas is -CH2-. ® In this particular embodiment, a specific embodiment is a compound of formula (I) selected from the group consisting of: Γ-(diphenyl fluorenyl)-6,7-dihydro-5H-spiro [biting mers [3, 2_g]decene oxime]_ 2'(ΓΗ)-ketone; 6,7-dihydro-5Η-spiro[吱,[3,2-g] acetylene-3,3'-θ丨嗓]-2 , (1Ή)-ketone; or 1-[(2R)-tetrahydrofuran-2-ylmethyl]-6,7-dihydro-5Η-spiro [> Furan[3,2-g] Bite 浠-3,3'- 哚 哚;|-2'(1Ή)-ketone. Another embodiment of the invention is a compound of the formula (Π) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is a compound of formula (II) wherein each R3a is hydrogen. In this particular embodiment, another specific embodiment is a compound of formula (II) wherein each Rsa is a fluoro group. In another embodiment, 'another embodiment is a compound of formula (9) selected from the group consisting of: 4-bromo-2-oxo[[,3,3-f][l,3]benzo[ Oxygenated terpene _7,3,_4丨143924-SP-20091127-1 •77· 201020257 嗓]-1'(2Ή)-|^acid third-butyl ester; 1'-{[2,5-two Methyl-1-(ι_曱ylethyl)_ΐΗ_pyrrol_3_yl]methyl} snail[吱,[2,3-f][l,3] bis(oxygen) 7,3'-ρ 嗓]_2'(ι'η) ketone; 7'-bromo snail [吱,[2,3-f][l,3]benzodioxolene-7 , 3'-noise]-2,(lΉ)-ketone; 1·-[(3-isopropylisoxazole_5_yl)methyl] snail [weiran[2,3-f][ l,3]benzodioxol-7,3'-吲哚]-2,(1,11)-one; bromo-2-indolyl)methyl]spiro[furan Benzodioxanthene-7,3'-吲哚]-(()-one; Γ-(1-benzofuran-2-ylmethyl) snail [吱 并[2,3- f][l,3]benzodioxanthene-7,3'-port 5丨哚]-2'(1Ή)-one; Γ-{[2-methyl-5-(trifluoromethyl) )-1,3-carbazole _4_yl] fluorenyl} snail [吱,[2,3<1[1,3]benzodioxanthene-7,3'-吲嗓]-2 , (1,11)-ketone; l'-{[5-(4-phenylphenyl)-2-(trifluoroanthracene)吱) 吱 -3--3-yl]methyl} snail [吱,[2,3-f][l,3]benzodioxolene-7,3'-吲嗓]-2, (1Ή )-keto; l'-{[5-alkyl-1-indolyl-3-(tris-methyl)-1Η-ρ ratio.坐-4-基]曱基} snail [吱D南和[2,3<][1,3]benzodioxolene-7,3'-吲嗓]-2' (1,1^ -_; Γ-(5-methoxypyridin-3-yl)spiro[吱,[2,3-f][l,3]benzodioxol-7,3'-啕哚] -2'(1Ή)-ketone; Γ-(4-bromobenzyl) snail [bito-and-[2,3-f][l,3]benzodioxolene-7,3,_Ρ bow丨哚]-2'(1Ή)-ketone; l'-{[(2S)-5-ketotetrahydroρpyr-2-yl]methyl} snail [吱,[2,3_f][i , 3] benzodioxanthene-7,3'-throindole]-2'(1Ή)-one; (2'-oxyspiro[吱,[2,3-f][l,3] Benzodioxanthene _7,3·_μ卜朵]_ι·(2'Η)-yl) 143924-SP-20091127-1 -78- 201020257 acetonitrile; 7H trifluoromethyl)_Γ_{[5_( Tris-methyl)_2•furanyl]methyl} snail [biting and [2'3-f][l,3]benzodioxene _7,3,_蚓哚]_21(1 yang _嗣; 14(5-alkyl-2- far phenyl) fluorenyl]_71_(trifluoromethyl) snail [cough and stupid and dioxolene-7,3·,吲哚]-2, (1Ή)-keto; 14(2-isopropyl-1,3.carbazole-5-yl)methyl]_7,-(trifluoromethyl)spiro[,,[2,3-f][ l,3]benzodioxanthene _7,3,_w 哚]_2ι(1Ή)__ ; l'-[(2-isopropyl Base-1,3-oxazol-5-yl)methyl]spib-pyrano[2,3-f][l,3]benzodioxanthene-7,3,-吲哚] -2,(1Ή)-one; [1-cyclopropyl-3-(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxolene-7, 3<_吲p花]-1'(2Ή)-yl)propyl]aminocarbamic acid tert-butyl ester; r-[4-(indolylthio)hanyl]spiro[吱-benzobenzodioxole圜 圜 _7,3,^ 哚]-Td'H)-ketone; 3-(2'-oxaspiro[furo[2,3-f][l,3]benzodioxanthene- 7,3,5丨哚]-1,(2Ή)-yl)propanenitrile; Γ-[(2-Molyl-1,3-thiazol-5-yl)indolyl] snail [biting and merging [2, 3-f][l,3]benzodioxanthene-7,3'-吲哚]-2·(1Ή)-one; l'-{[2-amino-4-(trifluoroanthracene) N) pyrimidazole _5_yl]methyl} snail [吱,[2,3-f][l,3]benzodioxolene _7,3·,丨哚;|_2·( Im·η) ketone; 4'-chloro-2'-oxo[[,3,6,6,6,6,5,5,5,5,5哚]-Γ(2Ή)-yl)acetonitrile; 1·-[(2-amino-1,3-thiasita-4-yl)indolyl] sirobf and [2,3-f][l , 3] benzodioxanthene-7,3'-啕哚]-2'(1':^)-sun; 4'-glycosyl-hydrazino-[(5-carbyl porphin-2- Base) Snail [吱,[2,3-f][l,3]benzone 143924-sp-20091127-1 -79- 201020257 Oxygen 圜-7,3'-θ丨嗓]-2'( 1'H)-Sig; l'-[(5-Acethiophen-2-yl)methyl]-2'-keto-oxime, 2'-dihydrospiro[furo[2,3-f] [1,3]benzodioxolene-7,3·-吲哚]-7·-carbonitrile; Γ-{[2-(1-methylethyl)-1,3-pyrazole- 4-yl]methyl}-2,-keto-oxime, 2,-dihydrospiro[furo[2,3-f][l,3]benzodioxene-7,3·-吲哚]-7·-carbonitrile; gas-based-Γ-[(5-chloropyrimidin-2-yl)methyl]spiro[吱,[2,3-f][l,3]benzo Dioxin, -7,3'-<嗓]-2'(1Ή)-one; 4'-chloro-1'-{[5-(trifluoromethyl)-2-furanyl] } 螺 & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & -1,3-Oxazol-4-yl)methyl] snail [吱,[2,3 rhyme 13]benzodioxanthene-ene-7,3·-啕哚]-2'(1Ή) -_ ; 4-[6-(monomethylamino)ρ than 唆_3·yl]·ι'_{[2-(ΐ-methylethyl) sevyl]methyl} snail [2,3-f][l,3]benzodioxanthene _7,3,_ρ?丨哚]_2,(1Ή)_ ketone; 1 -[(5-alkyl-1,2 , 4-pyrazolyl)methyl]spiro[吱,[2,3-f][i,3]benzodioxanthene-7,3'-p5丨p]-2' (1Ή)-嗣; 4'-Chloro-indole-[(5-alkyl-1,2,4-ρ-oxadiazolyl)methyl]spiro[furo[2 3 f][1,3] Benzodioxolanes-7,3'-吲嗓]-2, (;1,1^,; Γ-(4-oximeyl) snail [吱,[2,3_mi,3] Benzodioxolene-7,3,蜊哚]-2'(1Ή)-one; l'-[(2S)-l,4-dioxaindole-2-ylmethyl] snail Methyl benzodioxol-7,3'-啕哚]-2'(1Ή)-one; Γ-[(2-carbyl-U-, ethazol-5-yl) fluorenyl] snail [吱喃和[2,3_饥13] stupid and dioxolene-7,3'-啕哚]-2,(1Ή)-one; 143924-sp-20091127-l • 80 · 201020257 methylamine Base, 3·carbazole _5-yl]methyl snail [吱,[2,3-f][l,3]benzo-oxo- oxene-7,3'-noise]_2, (ιή)-ketone; [(2-moffolin-4-yl-indole, 3-carbazole-5-yl)methyl] sulphate benzodioxanthene _7,3'-吲嗓] -2,(1Ή)-ketone; 1 -[(2-hexahydroindole sigma small base 喧β sit: yl) methyl] snail [biting nucleus 3] benzodioxolene _7 ,3,-吲哚]-2,(1Ή)-ketone; 1 [(2methoxy-1,3-喽 _ 5 _ _ _ _ 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 5 Mercaptopurine, 2,4-4 di-sialyl]ethyl) snail [吱嗔3[2 3_叩, $ benzodioxene _7,3,_吲哚]_2, (1Ή) __ ; 4 chloro-1 -{[5-(difluoromethyl)+2,4-oxadiazole_3•yl]methyl} snail[吱,[2,3-η[1'3] Benzodioxolene-7,3,_啕哚]_2, (m) ketone; 4-alkyl-1-[(5-cyclopropyl-u,4 oxadiazole-3-yl)methyl] Snail [bitillates [2'3-f][l'3]benzodioxolene κ哚]_2, (1Ή) ketone; 4 chloro-1 -{1-[5-fluoromethyl) _u,4吟二唾基基]Methyl} sulphate φ [2,3-f][1,3]benzodioxolene-7,3,-巧哚]-2'( 1Ή)-ketone; ([5 (-Imethyl)-1,2,4-oxadiazole _3_yl]methyl} snail [味喃[2,3那,3] 本一一氧园-7,3Ί嗓]-2,(1Ή)-ketone; [(5 first butyl-no oxadiazole) fluorenyl] snails smashed and sputum, 3] benzo-oxo Benzene·7,3'-ρ 嗓]_2'(1'Η)-ketone; 1 -[(5-cyclopropyl-l,2,4-oxadiazolungyl)indolyl]spiro[furan Benzo-oxo-oxo-salt-7,3,-吲嗓]_2'(i,h )-ketone; 4_gas-group-1'-{[5-(1-methylethyl)-1,2,4-oxadiazol-3-yl]methyl} snail [唉 并[2' 3-f][l,3]benzodioxolene-7,3,old oxime]_2,(1Ή)_one; 143924 potential 20091127-1 -81 · 201020257 1 _{[5-(l- Methyl ethyl)-1,2,4-^ No.2. -3--3-yl]methyl} snail [biting and [2,3_f][i,3] benzodioxol-7,3'-吲哚]-2|(1)-one; L'-[(4-Methylhexahydropyrrolidin-1-yl)indolyl] snail [recommended benzodiazepine benzodioxanthene-7,3'-啕哚]-2' (1Ή )-ketohydrochloride; 1-[(3-methyl-2-indolyl-1,3-tetrahydrosodium β-s--5-yl)methyl] snail [biting s-[2,3-f] [i,3] benzodioxolanes-7,3·-吲哚]-2'(1Ή)-one; 1 -{[5-(dimethylmethyl)-!, 2,4-ρ 〇 〇 -3- 基 ] ] 甲基 -3- -3- -3- -3- -3- -3- -3- -3- -3- 2 2 2 2 2 2 2 2 2 2 2 2 2 -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- -3- Ν-Isopropyl-3-[2-(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxole _7,3,-吲哚]- Γ(2Ή)-yl)ethyl]hexahydropyridine small carboxamide; 5-[(2'-oxaspiro[furo[2,3-f][l,3]benzodioxanthene- 7,3,-吲哚]-l,(2,H)-yl)indenyl]p-cetin-3- bet; 2·-keto-1,2'-dihydrospiro [2,3-f][l,3]benzodioxanthene m 哚]-71-carbonitrile; N-methyl-5-[(2'-oxaspiro[吱,[2,3 -f][l,3]benzodioxanthene_7,3,_<哚]-Γ(2Ή)-yl)methyl]-2-(trifluoromethyl)-amino-3-carboxylate醯5-[(2'-oxaspiro[furo[2,3<][1,3]benzodioxol-7,3,-啕哚]-1|(2,1^- group ) 曱]]-2-(trifluoromethyl)?&#;South-3-treazone; Ν,Ν-dimethyl-5-[(2·-oxo[[,3,3] -f][l,3]benzodioxanthene _7,3'-吲哚]-Γ(2Ή)-yl)indolyl]-2-(trifluoromethyl)pyran-3-carboxylate Indoleamine; Ν-cyclopropyl-2-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxanthene knives, 3, _, bow 丨哚-1 '(2Ή)-yl)methyl]-1,3-oxazol-4-carboxyguanamine; N-(l-mercaptoethyl)-2-[(2·-oxo[pyrene] And [2,3-f][l,3]benzodioxanthene-7,3.?丨哚]-Γ(2Ή)-yl)methyl]-1,3-oxadazole-4- Carboguanamine; 143924-sp-20091127-1 -82· 201020257 Γ-[(5-chloro-2-pyrimenyl)methyl]_4,_[6-(dimethylamino)pyridine_3_yl] Snail [furo[2,3-f][l,3]benzodioxanthene_7,3,_β 哚; 14(5-alkyl-2·,exepyl)methyl-mesanyl Snail [吱) and (3) benzodioxanthene _7,3,-吲哚]-2,(1Ή)-one; and 4'-[6-(dimethylamino)pyridine-3- Snail [furo[2,3-f][l,3]benzodioxanthene-7,3'-啕哚]-2 (1Ή)-ketone; 2.2-di-failure-Γ-{[5-(trifluoroindolyl ketone-2-yl)indolyl} snail [吱,[2,3_耶,3] benzodiazepine Oxytene-7,3,-峋哚]-2,(1Ή)-one; ® 2,2-difluoro-1'-indole [5-(trimethylsulfonyl)-pyran-2-yl]曱基} snail [吱,[2,3-f][l,3] benzodioxene-7,3,-吲哚]-2,(1Ή)-one; 2.2-difluoro- Γ-{[3-(Trifluoromethyl) ρ-pyridinyl-2-yl]methyl} snail [吱 并[2 3_耶,3] benzodioxolan oxime-[(3- gas喽 喽 -2--2-yl)methyl] snail [bito-and [2,3-f][l,3] benzodioxos-ene-7,3'-蚓哚]-2, (1Ή) -ketone; Γ-{[3-(2,6-diphenyl)-5-methylisoxazole-based]methyl}spiro[furo[2,3〇[1,3]benzodioxole圜 圜-7,3·- 哚 哚]-2'(1Ή)-ketone; 1-({2-[4-(difluoroindolyl)phenyl]_ι, 3_ρ塞β坐_4-基} Scorpion) snail [biting α南和[2,3-f][l,3]benzodioxolene-7,3'_啕哚]-2·(1Ή)-one; l'-[ (5-phenyl-1,3,4-oxadiazol-2-yl)methyl]spib-[2,3-f][l,3]benzodioxol-7, 3'-啕哚]-2'(rH)-ketone; Γ-{[5-(4-chlorophenyl)_ι, 3,4-oxadiazol-2-yl]methyl} snail [puffan [2,3-f][i,3]benzodioxol-7,3'-W哚]-2'(1Ή)-one; Γ-([1,3] oxazolo[4 ,57>bipyridin-2-ylindenyl)spiroben[2,3-f][l,3]benzodioxolene-7,3'-啕哚]-2' (1Ή)-ketone; 143924-SP-20091127-1 -83· 201020257 (7S) chlorin-3-yl-indole-methyl snail [biting mers [2,3-], 3] benzodiox圜 -7-7,3'-嘀哚]-Τ(ΓΗ)-ketone; (7R)-4·-吱an-3-yl-Γ-曱-based snail [吱,[2,3-f] [l,3] stupid and dioxo-indole -7,3'-啕嗓]-2·(1Ή)-ketone; (7R)-#-bromo-indole-indoleyl snail [味喃[2 , 3-f][l,3] stupid and dioxin, _7 3, _ 啕哚]-2'(1Ή)-ketone; (7S>4'-> odor-based-methyl-spiro [ρ矢η南和[2,3-f][l,3]benzodioxanthene _7,3,_ρ丨哚丨哚]-2'(1Ή)-ketone; (7S)-4· -N--3-yl spiro[吱,[2,3-f][l,3]benzodioxolene-7,3,4丨哚]-2'(1Ή)-one; 7R)-4'_furan-3-yl snail [吱,[2,3-f][l,3]benzodioxene _7,3,_Ρ?丨哚]-2\1Ή) -ketone; Γ-methyl-4'-(tetrahydrofuran-3-yl)spiro[吱,[2,3-f][l,3]benzodioxanthene-7,3'-吲哚]-2'(1'11)-ketone Or 6-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxolene-7,3,_4 哚]_Γ(2,Η)_ base) Methyl]pyrimidine-2,4(1Η,3Η)-dione. Another embodiment of the invention is a compound of formula (III) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is a compound of formula (111) wherein each R6 is independently hydrogen, carbyl, bromo, fluoro, methyl, cyano, amine, -C(0 H, -CH2-N(CH3)2, (tetrahydropyrrolidin-1-yl)indolyl, 6-(dioxamicyl aridin-3-yl, 2-(4-fluorophenyl)vinyl, Dimethane[b,d]pyrimen-4-yl, benzopyrim-3-yl, 1-methyl_1H-rhodium-5,yl,3,5-bis(trifluoromethyl)benzene Base, 4-phenoxyphenyl, 4-(2-mercaptopropoxy)phenyl, 4-butoxyphenyl, 4-anthracene 143924-SP-20091127-1 -84- 201020257 π密π定-5-yl or p-pentan-3-yl. In this particular embodiment, another specific embodiment is a compound of formula (HI) wherein two R6 are adjacent to each other The carbons together form a fused dioxylyl alkenyl ring or a fused pyridyl ring. In this particular embodiment, another specific embodiment is wherein L is -Ο- and Μ is _CH2 A compound of formula (III). In this particular embodiment, a specific embodiment is a compound of formula (ΠΙ) selected from: • (3R)-5,6-dihydrospiro[benzo[l,2 -b : 5,4- b,]difuran-3,3,-吲哚]-2, (ΓΗ>ketone; (3S)-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,] Difuran-3,3W|哚]-2,(1Ή)-嗣; 1-0荅耕-4-ylindenyl)-5,6-dihydrospiro[benzo[i,2-b: 5, 4-b,]difuran-3,3'-啕哚]-2'(1Ή)-one; 4'-aero-1'-(diphenylfluorenyl)-5,6-dihydrospiro[benzene And like seven: 5, 4 seven] difuran _3,3, _ 吲哚]-2' (1 Ή)-ketone; 1 ·-(diphenylmethyl)-5'-fluoro-5,6-di Hydrogen snail [benzo[nb : 5,4_b,]difuran_3 3,_ 吲哚]-2'(1Ή)-one; 1-(phenylindenyl)-6'-fluoro-5,6 - dihydrospiro[benzo[nb : 5,4 b,]difuran_3 3,_ 吲哚]-2 丫1Ή)-one; 7'-aero-1'-(diphenylmethyl)- 5,6-digastric snail [stupid [ca: 5,4 b,] dioxin _3,3,_ 吲哚]-2'(1Ή)-ketone; 1, benzoquinone Η'-fluorine Τ-Τ-fluorenyl, 5,6-dihydrospiro[benzo[u_b: 5,4_b,]dipyran-3,3'-radaffin]-2\1Ή)-one; [-(diphenyl曱基^-Fluoro-based chlorinated dihydroanthracene...,, & mouth [stupid [l,2-b: 5,4-b]difuran-3,3'-吲哚]-2' (1Ή) -ketone; 143924-SP-20091127-1 〇s 201020257 6-((5-(Trifluoromethyl)furanyl)methyl)_2 3,5, 6, · tetrahydro 2 snail [[μ] dioxo ortho-conclusion [2,3-fH丨嗓_8,3, benzofuran [6 5 VII] furan _ ketone; 6-( ((R)-tetrahydrofuran-2-yl)methyl)_2,3,5,6,-tetrahydro-2-indole-spiro[[1,4]dioxolynene[2,3-fH丨哚-8,3'-benzofuro[6,5-b]furan]_7(6Η)-one; 4'-chloro-5,6-dihydrospiro[benzo[i,2-b: ketone 5'-Fluoro-5,6-dihydrospiro[benzo[i,2-b: ketone; 6'-fluoro-5,6-dihydrospiro[benzo[1,2-7: ketone; 7'-gas-based-5,6-dihydrospiro[benzo[i,2-b: ketone; 7'-fluoro-5,6-di-argon][benzo[1,2-7:5,4_b ']difuran-3,3'-啕哚]-2·(1Ή)-5,4_b']difuran-3,3'-,?丨哚]-2·(1Ή)-5,4-b ']difuran_3,3,_吲哚]_2,(1Ή)_ 5,4·β]difuran-3,3'-啕哚]-2'(1Ή)-5,4_b']difuran -3,3Μ丨哚]-2'(1Ή)-ketone; 4-ranyl-7-mercapto-5,6-monohydrospiro[benzo[i,2_b : 5,4-b,] two bites Drink _3,3'-mouth bow|哚]-2'(1Ή)-ketone; Γ-(tetrahydro-2Η- shout-2-ylmethyl)-5,6-dihydrospiro[benzo[七:5,4七,]difuran-3,3'-throindole]-Ζ(1Ή)-one; Γ-[(2-carbyl-1-indolyl-1Η-imidazole-5-yl) Methyl]·5,6_dihydrospiro[ Stupid [u_b : 5,4-b']difuran-3,3'-啕哚]-2'(1Ή)-_ ; l'-[(2R)-tetrahydrofuran-2-ylindenyl]-5 ,6-dihydrospiro[benzo-like seven:5,4_b,]dipyran-3,3'-啕哚]-2'(1)-one; 1-(3-methylbutyl)- 5,6--Wind snail [benzo[i,2-b : 5,4-b,]di-p-嗔-3,3,-p-bow|哚]-2'(ΓΗ)-ketone; 143924- Sp-20091127-1 •86- 201020257 1,-[(2S)-Tetrachloromethane-2-ylmethyl]_5,6-dihydrospiro[benzo[12-7:zhou]difuran-3,3 ^吲'•朵]-2\1Ή)-ketone; 1 -(tetrahydro-2Η-jung-4-ylindenyl)_5,6-dihydrospiro[benzo[12_b: 5 4 七,]二Bite -3,3'-p?l pk ]-2'(l'H)-Sl ; HP keto-5,6-dihydrospiro[benzo[U-7:5,]difuran_3 , 3W丨哚Η,(2Ή)_yl)methyl]furan-2-carboxylic acid methyl ester; l'-(l,4-dioxolyl-2-ylmethyl)_5,6-dihydrospiro [Benzo[u-b: 5,4_b,]difuran-3,3^5丨嗓]-2'(1Ή)-one; ® Γ-{[1_mercapto-3_(trifluoromethyl) -1H-pyrazolyl]indenyl}-5,6-dihydrospiro[benzo[l,2-b. 5,4-b']di-n--3,3'-吲嗦]-2 '(ι'η)-ketone; Γ-(tetrachloro-2Η-«ranyl-3-ylmethyl)_5,6-dihydrospiro[benzo[nb:5,4-7]difuran-3 , 3 -啕哚]-2·(1Ή),; 2-[(2'-fluorenyl-5,6-dihydrospiro[benzo[12_b:5,4heptanfuran_3χ哚]]) Methyl]-1,3-oxazole-4-carboxylic acid methyl ester; 1-(2-capped mercapto)-5,6-dihydrospiro[benzo-like seven:5,4-b,]difuran- 3,3,-W哚]-2'(1Ή)-ketone; gin 1'-(4-fluoroaryl)-5,6-dihydrospiro[benzo[u_b:5,4-b·] Furan-3,3,-W 哚]_ 2'(1Ή)-one; Γ-knot group-5,6-dihydrospiro[benzonb: 5,4_b,]difuran_3,3,_w 哚]_2,(1,Η)_ ketone; Γ-(linked stupid_4_ylmethyl)_5,6-dihydrospiro[benzo[u-7:5,4-7,]difuran_3,3, _吲哚]-2·(1Ή)-ketone; 1'-(tetrahydro-n-yl-3-ylindenyl)_5,6-dihydrospiro[benzo-like seven:5,4,7,]difuran- 3,3·-吲哚]-2·(1,Η)-ketone; 143924-sp-20091127-1 201020257 1 -[(3->Smellyisoxazole-5-yl)methyl]_5, 6-dihydrospiro [benzo with 27:5 4,] difuran-3,3'-4 哚]-2'(1Ή)-one; 1 -[(5-> stinky bite- 2-yl)methyl]-5,6-dihydrospiro[[b][12b:5 4_bi]difuran-3,3,-thirsty]-2,(1Ή)-one; Γ-(tetrahydrofuran- 2-ylindenyl)_5,6_di-argon snail [stupid [to seven:5,4 b,]difuran-3,3 '-嘀哚]-2'(1Ή)-ketone; Γ-(propylene oxide-2-ylindenyl)-5,6-dihydrospiro[benzo[u_b:54,7]difuran-3, 3'-蚓哚]-2'(1Ή)-_ ; Γ-[(1-ethyl-1ΗΚ5-yl)methyl]_5,6-dihydrospiro[benzo[12:54b,]difuran -3,3'-吲哚]-2'(1Ή)-one; 3-[(2-keto-5,6-monohydrospiro[benzo[1,2-7:5,4-b.] : bite--3,3Wh stays]-1,(2Ή)-yl)mercapto]benzonitrile; 4-((2'-keto-5,6-dihydro-2Η-spiro[benzofuran [6 5 b]furan_3,3,dihydroanthracene]-fluorenyl)methyl)benzonitrile; 4,-[(2,-keto-5,6-dihydrospiro[stup [ U_b : 5,4 b,]difuran _3,3,_ (f) 哚]-Γ(2Ή)-yl) fluorenyl]biphenyl-2-indene nitrile; l'-{(2S)-2-[ (yloxy)methoxy]propyl b 5,6-dihydrospiro[benzo[i 2 b : 5 state difuran-3,3'-fluorene]-2'(1Ή)-one; -(2,3-dihydro-1,4-benzodioxanthene-6-ylmethyl)5 6 dihydrospiro[benzo[l,2-b . 5,4-b'] ρ失喃-3,3'-叼| ρ朵]·2'(1Ή)-ketone; Γ-(2,1,3-Benzene$ II) sit-5-ylindenyl)-5,6- Dihydrospiro [benzo[12_b: 5,4 b,]difuran-3,3·-clear]-2'(1Ή)-嗣; l'-(2,l, 3-benzothiazolidine-5-ylindenyl)-5,6-dihydrospiro[benzo[12_b:5 4 b,]difuran-3,3'-啕哚]-2' (1' 11)-keto; 143924-SP-20091127-1 -88- 201020257 l'-[(4-Georofolf-2-yl)methyl]_5,6·dihydrospiro[benzo[12: 5,4,7,]difuran-3,3^呻哚]-2'(1Ή)-_ ; Η(2-_yl-5,6-dihydrospiro[benzo[7]5,4- b,]二吱喃_3,3'-port 5 noisy]-1'(2Ή)-yl)methyl]tetrahydroanthracene slightly small acid tert-butyl ester; (2S)-2-[(2 '_keto-5,6-dihydrospiro[stup [nb: 5,4-7,]difuran_3,3ι_ρ丨嗓丨嗓]-Γ(2Ή)-yl)methyl;|tetrahydropyrrole small Tert-butyl carboxylic acid; 4_[(2-keto-5,6-monohydrospiro[benzo[u-7:5,4七.]二咳喃_3,3,_吲哚]_r(2 ,H)_yl)indenyl]hexahydroindole»by biting-1-acidic acid third-butyl ester; _ 4'-chloro-indole-{[5-(trifluoromethyl)pyran-2- Methyl}-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran_3,3·-叼卜呆]_2·(ι,η)_ Ketone; 4'-chloro-l'-[(2R)-izghydrofuran-2-ylmethyl]_5,6-dioxaspiro[benzo[nb:5,4-b']difuran-3 , 3'-4 哚]-2, (1Ή)-ketone; 4'-bromo-1'-[(21〇-tetrahydrofuranylmethyl)_5 6_ Dihydrospiro [benzo[[7:5,47'] diterpene-3,3'-called budu]_2, (1)-ketone; 144-(indolyl) _5,6-dihydrospiro[benzo[[7:5,4-b,]difuran-3,3^?丨哚]-2·(1Ή)-one; gin 1 -[(2-oxo)嘲 咬 -5-yl) fluorenyl]_5 6_ dihydrospiro [stupid [12 b : 5,4 b,] dipyran-3,3·-吲哚]-2'(1Ή)-ketone ; 7'-gas-l'-((5-(trifluoromethyl)furan-2-yl) fluorenyl)_5,6 dihydro-2 snail [stupid and sulphur [6,5-b Pf-am-3,3,-dihydrogen]_2'-ketone; (3R)-1 -(3-mercaptobutyl)-5,6-dihydrospiro[benzo[ub:5, 4-b1]difuran-3,3·,吲哚]-2'(1Ή)-one; (3 ft)-1-pentyl-5,6-dihydrospiro[benzo[1,2:7: 5,4,7,] 二吱"South_3,3'-吲嘴] 2,(1Ή)-ketone; 143924-sp-20〇9l 127-1 -89- 201020257 (3R)-l'-〇» Bis-2-ylmethyl)-5,6-di-argon[benzo[l,2-b: 5,4-b']di-p-amran-3 3,- 啕哚]-2' ( ΓΗ)-ketone; (3R)-l'-{[5-(trifluoromethyl)pyran-2-yl]methyl b 5,6-dihydrospiro[benzo[1 2-b : 5.4- b']difuran-3,3'-吲哚]-2·(1Ή)-one; (3S)-l'-〇 咬 -2--2-yl fluorenyl)-5,6-dihydrospiro[benzene And [l,2-b: 5, 4-b']二吱鸣-3,3'-吲哚]-2'(1Ή)-ketone; (3S)-1 -{[5-(difluoroindolyl)pyran-2-yl]- 5b,6-dihydrospiro[benzo[i,2_b : 5.4- b·]difuran-3,3'-吲哚]-2'(1Ή)-one; 7- disorder-1-[ (211)-Tetramonium-2-ylmethyl]-5,6-dihydrospiro[benzo[i,2_b: 5.4-b]difuran-3J-吲哚]-2'(1Ή) -ketone; 7'-fluoro-l'-[(2R)-rahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo-like seven: 5.4-b']difuran-3 , 3'-(9)哚]-2·(1Ή)-ketone; 41-fluoro-71-fluorenyl-r-[(2R)-ra-hydrofuroxime-2-ylmethyl]-5,6-di Hydrogen snail [benzo[l,2-b: 5,4-b'] bismuth sulphate-3,3'-purine]-2'(1Ή)-one; 1 -[2-(2- Methoxyethoxy)ethyl]_5,6-dihydrospiro[benzo[1,2-7:5,4-b,]dioxan-3,3'-吲哚]-2' (1Ή )-ketone; 1 -{[(2S)-5-S-iso-tetrahydropyrrol-2-yl]methyl}-5,6-dihydrospiro [stupid [1,2 7: 5.4- b'] Difuran-3,3·-吲哚]-2,(1,H)-one; Γ-[2-(2-keto-1,3-tetrahydrocarbazole-3-yl)ethyl]_5 , 6_ dihydrospiro [benzo[12 b : 5.4- b'] dipyran-3,3'-呻嗓]-2, (1,11)-one; l'-(4-pyridine-2 -benzylidene)_5,6-dihydrospiro [benzoan-like seven·· 5, 4_b,]difuran_3 3,_蚓哚]-2'(1Ή)-one; Γ-(pyrimidin-2-ylmethyl)-5,6-dihydrospiro [benzoan-like seven:5,4_b ,]difuran_3,3,啕哚]-2\1Ή)-ketone; 143924-sp-20091127-1 •90- 201020257 1 -(Cyridin-4-ylmethyl)-5,6-dihydrogen Snail [benzo[12_b: 5,4-7,]difuran_3,3Lii?丨哚]-2'(1Ή)-one; 1·7 than tillage_2_ylmethyl)-5,6-di Hydrogen snail [benzo[u_b : 5,4-7,]difuran_3,3,_ρ5丨哚]-2'(1Ή)-one; 1 -[(7-fluoro-1-benzofuran_2 ·Methyl]_5,6-dihydrospiro[benzo[12 b: 5 4 b,] difuran-3,3·-吲哚]-2,(1Ή)-嗣; Γ-(嗒耕-3-ylindenyl)-5,6-dihydrospiro[benzo[[7:5,4-7]) 2 (3,3,啕哚]-2'(1Ή)-one; _ Γ- [(2-keto-1,3_tetrahydrocarbazol-5-yl)methyl]-5,6-dihydrospiro[benzo[i,2-b:5.4-b']difuran-3 ,3Ί 嗓]-2,(1Ή)-_ ; Γ-[3-(oxy)indolyl]-5,6-dihydrospiro[benzoh-y-2:5,4-b,]difuran _3,3,_ 哚 哚]-2'(1Ή)-ketone; Γ-[(1-methyl-1Η-benzimidazole_2-yl)methyl]_5,6-dihydrospiro[benzo [U b : 5.4- b] difuran-3,3'-啕哚]_2, (ΓΗ)-ketone; Γ-(2Η-benzophenone Zin-2-ylindenyl)_5,6-dihydrospiro[benzo[u_b: 5 4 b,]difuran-3,3*-called | 嗓]-2*(1Ή)-one; 2- [ (2'-mercapto-5,6-dihydrospiro[benzo[1,2:7,5,7'] diterpene-3,3·-〃!丨嗓]-1·(2Ή)- Methyl]methyl benzoate; 3-[(2'-keto-5,6-dihydrospiro[phenyl][i,2_b: 5,47']difuran_3,3,_巧哚]_ι,(2Ή)-yl)methyl]benzoic acid vinegar; 4-[(2'-keto-5,6-dihydrospiro[benzo[丨,2:7:54_b^furan_3, 3, _ 巧 哚 pwH) - yl) methyl] benzoic acid methyl vinegar; 1 · -[3-(decyloxy) propyl]-5,6-dihydrospiro [benzo[i,2-b : 5,4-b,]difuran-3,3W| 哚]-2'(1Ή)-one; 143924-sp-20091127-1 -91 - 201020257 Fluoro-r-[(2R)-rahydrofuran _2-ylindenyl]-5,6-dihydrospiro[benzo[12_b:5.4-b']difuran-3,3'-吲哚]-2'(1Ή)-one; 6-dan 1 Base-1-[(2 ft)-tetraquinone 〇Nan-2-ylmethyl]-5,6-dihydrospiro[benzo[12-1): 5.4- b']difuran-3,3 '-吲哚]-2'(1Ή)-ketone; 1 -(hexahydro'» than -4-ylmethyl)-5,6-dihydrospiro[benzo[1,2:7:5,4 -b'] Diterpenoid-3,3'-啕哚]-Τα'Η)-one; mercaptoethyl)hexahydropyridin-4-yl]曱基卜 5,6_Dihydrospiro[benzo[l,2-b : 5,4-b']dioxan-3,3'-吲ρ朵]-2'(1Ή)-_ hydrochloric acid Salt; Γ-[(1-ethylhexahydron-4-yl)methyl]-5,6-dihydrospiro[p- and [7:5,4-b,] ® difuran-3, 3'-吲哚]-2'(1Ή)-class; Γ-[(1-mercaptohexahydropyridin-4-yl)indolyl]-5,6-dihydrospiro[benzo[r], 2_b: 5 , 4,7,]difuran-3,3'-吲哚]-2·(1Ή)-one; l'-[(2S)-tetrahydropyrrole-2-ylindenyl]-5,6-dihexane Snail [benzo[i,2_b : 5,4-b,]dipyran-3,3·-吲哚]-2'(1Ή)-one; 3-[(2-keto-5,6- a snail [benzo[i,2-b: 5,4-1)'] two-nose--3,3^5-b]-1'(2Ή)_yl)methyl]benzoic acid; -{4-[5-(Trifluoromethyl)-1,2,4-oxadiazol-3-ylhexyl}·5,6·dihydrospiro[benzone [l,2-b : 5 , 4-b'] 吱口口南-3,3.-^1 嗓]-2,(1Ή)-嗣; l'-[4-(5-methyl-1,2,4′′ diazole -3-yl) aryl]]5,6-dihydrospiro[benzopyrene, 2_b: 5.4-b']difuran-3,3·-吲哚]-2Χ1Ή)-one; Γ-[(5- Ρ-pyridin-4-ylfuran-2-yl)indolyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3'-啕哚]-2'(1Ή)-ketone; Γ-(4-pyridin-3-ylindenyl)- 5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-吲哚]-2'(1Ή)-one; 143924-SP-20091127- 1 _ 92 -

201020257 Γ-[(2'-Fluorobiphenyl-4-yl)methyl]_5,6-dihydrospiro[benzo[u_b: 5,4-7,]difuran-3,3'-mouth 哚]-2,(1Ή)-ketone; l'-[3-(5-methyl-1,2,4-oxadiazole-3-yl)benzyl]_5,6-dihydrospiro[benzo[ 12 b : 5.4- b] dioxin]_2,(1Ή)-one; 1'-{3-[5-(trifluoromethyl)-l,2,4-oxadiazole_3_yl]贵基}-5,6-二氲螺[Benzo[l,2-b ·· 5,4-b']disole _3,3,-θ budo]-2,(1Ή)-ketone ; l'-[4-(5-Methyl-4Η-1,2,4-triazol-3-yl)benzyl]_5,6-dihydrospiro[benzo[12: 5.4- b'] Dimethane-3,3'-啕哚]_2,(ΓΗ)-_ ; 2-2-[(2__基_5,6_Dihydrospiro[benzo[1,2:7,5,7,7] Dimethane-3,3,_吲哚]1(23⁄4). yl)methyl]benzoic acid; 4-[(2'-keto-5,6-dihydrospiro[benzo[U_b: 5, 4,7,]difuran_3,3,?丨哚Η,(2Ή)_yl)methyl]benzoic acid; Γ-(3-hydroxypropyl)-5,6-dihydrospiro[benzo[u —b : 5,4-b,]difuran_3,3,_吲哚]. 2\1Ή)-one; 2'-keto-l'-[(2R)-rahydrofuran_2-yl Thiol]_r,2,,5,6_rahydrospiro[benzo[[7:5.4-b']difuran-3J-4哚]_4'_carbonitrile; 2·-keto-l'-[( 2R)- Hydrofuran-2-ylmethyl: ^^^, tetrahydrospiro and ^27: 5.4-b']difuran-3,3'-β 哚]-4·-reindolaldehyde; 4'-[ (diammonium) fluorenyl]-r-[(2R)-eghydrofuran-2-ylindenyl]_5,6-dihydrospiro[benzo[l,2-b: 5,4-b' Difuran-3,3,-峋哚]-2·(1Ή)-net; 4'-(tetrahydropyrrole-1-ylmethyl)_i'_|; (2R)-tetrahydrofuran_2_ylindole Base]_5,6 dihydrospiro[benzo[l,2-b:5,4-b']di-puff-3,3'-bend]-2,(1Ή)-嗣; 4- Amino-l-[(2R)-eg fengfufufu-2-ylmethyl]-5,6-dihydrospiro[benzo[i,2_b : 5.4- b']difuran-3,3' -吲哚]-2'(1Ή)-ketone; 143924-sp-2009l 127-1 •93· 201020257 1'-(morpholin-2-ylmethyl)-5,6-dihydrospiro[benzo [u-b: 5,4-b,]difuran-3,3,-丨哚]-2\1Ή)-one; 1-[(4-methylmorpholine-2-yl)methyl; |_5,6_Dihydrospiro[benzo[12-7:5 4,7]difurate-3,3'-吲嗓]-2'(1Ή)-net; 1 {[4 (1-methyl) Ethyl) ibufondene_2_yl]methyl b 5,6_dihydrospiro [benzo[12-7:5,4-b'] diterpenoid-3,3'-θbdu]_2' (1Ή)-keto; 1 -methyl-5,6-monohydrospiro[benzo[1,2-7:5,4-b.]dioxin_3,3.-吲哚]-2 (1Ή)-ketone; Γ-[4-(1Η-tetrazol-5-ylindenyl]_5,6-dihydrospiro[benzo[[7:5 4,7]difuran-3,3'-吲哚]-2Χ1Ή)-ketone; Γ-(3-hydroxybenzyl>5,6-dihydrospiro[benzo[u_b:5,4_b,]difuran_3,3,吲哚]_ 2' (1Ή)-ketone; Γ-(4-morpholine-4-ylindenyl)-5,6-dihydrospiro[benzo[12-7:5 4_b,]difuran_3 3,_ 41 哚] -2 丫1Ή)-ketone; Γ-(tetrahydropyrrol-3-ylindenyl)-5,6-dihydrospiro[benzo[u_b:54,7]difuran-3,3W 丨哚]-2 '(1Ή)-ketone; Ν-σ-methylethyl m(2,-_yl-5,6-dihydrospiro[benzo[ca]·5州二呋鸣-3'3W|哚]- 1,(2Ή)-yl)methyl]tetrahydropyrrole carboxycarboxamide; (3SH'-[(2R)-0 nitrobutan-2-ylindenyl]_5,6-dihydrospiro[stup [ To: 纠,] difuran-3,3W丨哚]-2'(1Ή)-one; (3RH,-[(2R)-tetrahydrocrylatemethyl]_5,6-dihydrospiro[benzo :5-State difuran-3,3'-吲哚]-2'(1Ή)-one; (3 Magic-14 Qing-Tetraflavor-2-ylmethyl)_5,6-Dihydrospiro[Benzene And [12 7:5 4 b,] difuran-3,3'-呻哚]-2'(1Ή)-one; 143924-sp-20091127-1 -94- 201020257 (3S)-r-[(2S )-w hydroquinone-2-ylmethyl]-5,6-dihydrospiro 7:54b,] difuran-3,3'-bend]-2"(1Ή)-ketone; 1'-{[(2S)-1-indolyl-5-ketotetrahydropyro-2 -yl]methyl}_5,6-dihydrospiro[p- and [l,2-b:5,4-b']difuran-3,3'-indolo]-2·(1Ή)-one Ν-(cyclohexyldecyl)-3-[(2·-keto-5,6-dihydrospiro[benzo[12_b: 5,4-7]]difuran-3,3'-吲哚] -1'(2Ή)-yl)indolyl]phenylhydrazine; Ν-(2-methoxyethyl)-3-[(2'-keto-5,6-dihydrospiro[benzo[ i,2_b : 5,4-b']·^ gnaw-3, 吲哚]-Γ(2Ή)-yl) fluorenyl]phenylamine; ® Ν_ 己基善曱基[[2'- Keto- 5,6-dihydrospiro[benzo[l,2-b:5,4_b,]difur. South-3,3·-吲哚]-Π2Ή)-yl)methyl]benzamide; N-(2-ethylbutyl)-3-[(2'-keto-5,6-di Hydrogen snail [benzo[1,2-7:5,4-b,]difuran-3,3W丨哚]-1·(2Ή)-yl)methyl]benzamide; Ν-(2,4 -didecylphenyl)-3-[(2'-keto-5,6-dihydrospiro[benzo[1,2:7,5,4-b']difuran-3,3'-啕哚]-1·(2Ή)-yl) fluorenyl]benzamide; 3-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4- b']二ρ夫喃_3,3'-p? Budu]-1·(2Ή)-yl)methyl]-indole-(2-phenylpropyl)benzoquinone; ® N-[ (1S)-1-cyclohexylethyl]-3-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3 , 3'-(4)哚]-1'(2Ή)-yl)indolyl]benzamide; N-[(1RH-cyclohexylethyl]-3-[(2'-keto-5,6-) Dihydrospiro[benzo[i,2-b : 5,4-b·]difuran-3,3'-吲哚Η·(2Ή)-yl)indolyl] abbreviated amine; >1- (4-ethylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7']difuran-3J-吲哚]- Γ(2Ή)-yl)methyl]benzamide; !^-(2-ethylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[1, 2-1): 5, 4 seven '] two 吱 -3 -3,3'-哚]-Γ(2Ή)-yl)methyl]benzamide; 143924-sp-20091127-1 -95- 201020257 N-(2,4c-decylphenyl)-2-[(Τ-keto- 5,6-dihydrospiro[benzo(10)7:5,4-7,]difuran-3,3·-啕哚]-1'(2Ή)-yl)indolyl]benzamine; Ν-( 2-oxooxyphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[u_b:5,4-7]]difuran-3,3·-啕哚]-1 ·(2Ή)-yl)methyl] alum; amine-(2-fluorophenyl)-2-[(2'--yl-5,6-dihydrospiro[benzo[[] 4,7,]di-pyran-3,3'-吲哚]-1'(2Ή)-yl)indolyl]benzamide; (3-chlorophenyl)-2-[(2'-ketone) Base-5,6-dihydrospiro[benzo[1,2_|;:5,4,7,]di-pyran-3,3'-吲哚]-1'(2Ή)-yl)indolyl] Clandoleamine; Ν-(3-fluoro-2-methylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b: 5, 4-b']difuran-3,3·-啕哚]-1'(2Ή)-yl)indolyl]benzamide; Ν-heptyl-2-[(2'-keto-5, 6-Dihydrospiro[benzo[i,2_b : 5,4-b,]difuran-3,3,-啕哚]-1·(2Ή)-yl)methyl]benzamide; 2-oxobenzyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]di'1-arab-3, 3'-吲哚]-Γ(2Ή)-yl)methyl]benzamide; hexahydropyridin-1-ylcarbonyl)benzyl]·5,6-dihydrospiro[benzo[^7:5 ,4 VII.] Difuran-3,3'-吲哚]-2'(ΓΗ)-one; Ν-butyl winter [(2,-keto-5,6-dihydrospiro[benzo[l] ,2-b : 5,4-b,]difuran-3,3,-蜊哚]-Γ(2Ή)-yl)indolyl]benzamine; (3-mercaptophenyl)-2 -[(2|-keto-5,6-dihydrospiro[benzo[1,2-7:5,4?|]difuran-3,3'-吲哚]-Γ(2Ή)-yl) Methyl]benzamide; Ν-(2-carbyl-5-mercaptophenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b] : 5,4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)indenyl]benzamide; (2,3-dimercaptophenyl)_2-[ (2|-keto-5,6-dihydrospiro[benzo[ubub:5,4-b,]difuran-3,3·-啕哚]-Γ(2Ή)-yl)methyl]benzene曱醯amine; 143924-sp-20091127-1 ·%· 201020257 N-[2_(4~methoxyphenyl)ethyl]-2-[(2·-keto-5,6-dihydrospiro[benzene And [i,2-b : 5,4-b,] difuran-3,3'-吲哚]-1,(2Ή)-yl)methyl] cumamine; team (3-gas narrow base) )-2-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran_3,3W)哚]_r(2'H)-yl)indolyl]phenylhydrazine; n_[2-(4-phenylphenyl)ethyl]_2_[(2'-keto-5,6-dihydrospiro[ Benzo[i,2-b:5,4-b,]difuran-3,3W丨哚]-1'(2Ή)-yl)methyl]benzamide; Ν_(2-methoxyphenyl) )-4-[(2'-keto-5,6-dihydrospiro[benzo[i,2_b : 5,4-b,] dioxin _3,3'-吲哚Η' (2Ή) -yl)mercapto]phenylamine; ❹4-[(2-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']dioxan-3 , 3^5丨嗓]-Γ(2Ή)-yl)methyl]-indole-[2-(trifluoromethyl)phenyl]benzamide; 4-[(2-keto-5,6 -Dihydrospiro[benzo[l,2-b: 5,4-b']dioxan-3,3'-ρ5 budo]-1,(2Ή)-yl)methyl]-anthracene-benzene Benzoguanamine; Ν-mercapto-4-[(2'-indolyl-5,6-dihydrospiro[benzo[l,2-b:5,4,7]] ,3,-吲哚]-Γ(2Ή)-yl)indolyl]benzamine; Ν-(2-murinephenyl)-4-[(2'-keto-5,6-dihydrospiro) [Benzo[i,2-b : 5,4-b']diindole-33-吲哚]-Γ(2Ή)-yl)methyl]benzamide; Φ 4-[(2'- Keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b.]dimethane-3,3^5丨嗓]-1'(2Ή)-yl)methyl ]-Ν-(2-嚓-phen-2-ylethyl)phenylhydrazine 4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3,-吲哚]-1, ( 2Ή)-yl)methyl]phenylhydrazine; Ν-(2,3-dihydro-1Η-莽-5-yl)-4-[(2'-keto-5,6-dihydrospiro[ Benzo[i,2-b:5,4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzamide; Γ-[4-(? Fusolin-4-ylcarbonyl)-yl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3'-吲哚]-2_( 1Ή)-ketone; 143924-SP-20091127-1 •97- 201020257 N-(2-ethylphenyl)-4-[(2'-mercapto-5,6-dihydrospiro[benzo[i, 2 7: 5, 4-b,] two bites. South-3,3'-吲哚]-1'(2Ή)-yl)methyl]benzamide; Ν-(2,6-diamidinophenyl)-4-[(2'-keto) -5,6-dihydrospiro[benzo[12_b:5,4-b,]di-butan-3,3'-p?bido]-1'(2Ή)-yl)indenyl]benzimidazole Amine·, Ν-(3- disordered phenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-b']di-brown- 3,3'-啕哚]-1'(2Ή)-yl)methyl] alum; 1^-(2,4-dimethylphenyl)-4-[(2'-fluorenyl- 5,6-dihydrospiro[benzo[7:5,4,7],difuran-3,3'-峋哚]-Γ(2Ή>yl)indolyl]clumamine; 4-[(2 '-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]dioxan_3,3Ί ρ-]-Γ(2Ή)-yl)methyl] -Ν-0»cephen-2-ylmethyl)phenylhydrazine; Ν-ethyl-4-[(2'-keto-5,6-dihydrospiro[benzo[1,2 seven: 5,4-b']dipyran-3,3,-吲嵘]-Γ(2Ή)-yl)indolyl]benzamine; Ν-(2-methoxyethyl)-4-[ (2'-keto-5,6-dihydrospiro[benzo[!,2-b : 5,4-b']difuran-3,3'-啕哚]-Γ(2Ή)-yl)曱-]benzamide; Ν-(2-ethoxyethyl)-4-[(2'-keto-5,6-dihydrospiro[stup [[,,2-b: 5,4] -b']二味喃-3,3·-吲哚]-Γ(2Ή )-yl)methyl]benzamide; Ν-cyclobutyl-4-[(2-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b' Di-pyran-3,3-吲哚]-1(2Η)-yl)methyl]benzamide; 4_[(2'-keto-5,6-dihydrospiro[benzo[i, 2-b: 5,4-b']di-n-but-3,3W丨嗓]-1,(2Ή)-yl)methyl]-anthracene-1,3-p-conazole-2-ylphenylhydrazine Amine; Ν-(3-fluoro-2-methylphenyl)-4-[(2[keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b' Difuran-3,3Wbido]-1'(2Ή)-yl)methyl]benzamide; ]^-(2-ethylbutyl)-4-[(2'-keto-5) ,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzamide; 143924- Sp-20091127-l -98- 201020257 2-(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-7']di-p-am-3,3' -吲嗓]-1,(2Ή)-yl)acetamide; Ν-(4-ethylphenyl)-2-(2'-keto-5,6-dihydrospiro[benzo[i, 2-b: 5,4-b,]difuran-3,3W丨哚]-Γ(2Ή)-yl)acetamide; hydrazine, hydrazine-diethyl-2-(2'-keto-5 ,6-dihydrospiro[],[i,2_b:5,4-b1]difuran-3,3,-吲哚]-Γ(2Ή)-yl)acetamide; Methyl butyl)-2 -(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3,3'-啕哚]-Γ(2Ή)-yl)B Indoleamine; _methylethoxy)propyl]-2-(2'-keto-5,6-dihydrospiro[{,2-b:5,4-b]difuran-3 , 3'-吲哚]-Γ(2Ή)-yl)acetamide; 2-(2-mercapto-5,6-aza snail [本弁[l,2-b : 5,4-b' ] 2 bite shouting -3,3^5 Bu Duo]-Γ(2Ή)_ base)-Ν-propyl ethylamine; Ν-mercapto-2-(2·-keto-5,6-dihydrogen Snail [benzo[1,2:7,5,4,7],diazine-3,3·-吲哚]-Γ(2Ή)-yl)phenylacetamide; Ν-(2,5-- Nonylphenyl)-2-(2·-keto-5,6-dihydrospiro[benzo[丨丨:5,4-b']dioxan-3,3^吲哚]-1' (2)-yl)acetamide; N-(2,4-mercaptophenyl)-2-(2·-keto-5,6-dihydrospiro[benzo[beta]:5 4_b, Dioxam-3,3|-吲哚]-ΐ'(2Ή)-yl)acetamide; Ν-(2,3--methylphenyl)-2-(2'-keto-5 ,6-dihydrospiro[benzo[ab:5,4-b']dipyran-3J-吲哚]-Γ(2Ή)-yl)acetamide; Ν-(2,6--methyl Phenyl)_2-(2'-keto-5,6-dihydrospiro[benzo-7:5,4-b']dioxin-3J-吲哚]-Γ(2Ή)-yl)acetamidine Amine; 5-[(2-keto-5,6-dihydrospiro[ And [1,2 7:5,4-b']2,3·3·_ρ!丨嗓]_ι,(2Ή)-yl)methyl]pyran-2-carboxylic acid; 143924-SP -20091127-1 -99- 201020257 N'N-Dimercapto-5-[(2'-keto-5,6-dihydrospiro[benzo-like seven:5 4-7]]difuran_3,3 , _ 啕哚ΗΧ 2 Ή) - yl) methyl] fur. South 1 carboxamide; N-mercapto-5-[(2,-keto-5,6-dihydrospiro [stupid and like seven: 5 4 VII]] difuran)] Γ (2Ή) -yl)methyl]furan-2-carboxylate; 2-[(2'-keto-5,6-dihydrospiro[stuppy[υ7:5,4-7]difuran-3,3,啕哚]_r(2,H)_yl)methyl]-1,3-oxazol-4-carboxyguanamine; N,N-dimethyl-2-[(2'-keto-5,6 -dihydrospiro[benzoxl,2:7,5,4-b,]difuran-3,3,-anthracene-1'(2Ή)-yl)indolyl]#嗤_4_treazone ; l'-[(2S)-2-Phenyl]-5,6-dihydrospiro[benzo[]L,2_b : 5,4_b,]difuran_3,3,_吲φ 哚]- 2'(ΓΗ)-ketone; 1'-[(28)-2-(decyloxy)propyl]-5,6-dihydrospiro[benzo[1,2:7,4,7,] Furan-3,3匕吲嗓]-2'(1Ή)-one; l'-{(2S)-2-[(4-)benzyl)oxy]propyl 5-,6-dihydrospiro[ Benzo[12_b:5,4-b,]difuranium]-2'(1Ή)-_ ; r-[(2S)-2-(acridin-2-yloxy)propyl]_5, 6_Dihydrospiro [Benzene like seven: 5, 4-7,] difuran-3,3'-吲哚]-2·(1Ή)-one; 1-(3-butyl)-5,6 -—Wind snail [本弁[l,2-b . 5,4-b']二咬喃-3,3'-叫丨ρ朵]-❿ 2'(1Ή)-ketone; Γ_(4,4 , 4-trifluoro-3- Butyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-♦]-2,(1Ή),; 3-( 2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-呻哚]-1,(2Ή)-yl) Propionaldehyde; Γ-{3-[(3-mercaptobutyl)amino]propyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b]difuran- 3,3'-吲哚]-2'(1Ή)-keto hydrochloride; 143924-sp-20091127-1 -100- (Si 201020257 1 ]3-[butyl(methyl)amino]propyl 5,6_dihydrospiro[benzopyrene-7:5 4-7,]di-n--3,3'-吲哚]-2'(1Ή)-ketohydrochloride; 1 -{3-[(2 '2,2-Trifluoroethyl)amino]propyl propyl 5,6-dihydrospiro[benzo[[7:5,4-b']difuran-3,3'-吲哚]-2 '(1Ή)-ketohydrochloride; 3-{[3-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran- 3,3,-noise]-1'(2Ή)-yl)propyl]amino}propionitrile hydrochloride; 4-[6-(monomethylamino)11 to bite_3_yl]_1' _[(2 feet)_tetrahydroflavor 0 South_2_ylindenyl]_5,6_dihydrospiro[本,[l,2-b : 5,4-b·]2 sniffer-3,3 '->»5卜朵]-2·(1Ή)-ketone; ® 4'-[(Ε)_2-(4-fluorophenyl)vinyl H'-[(2R)-tetrahydrofuran-2-yl methyl]_ 5,6-dihydrospiro[benzo[l,2-b:5,4-b']dipyran-3,3,-吲哚]-2'(1,11)-one; 4'- Dibenzoindene, (1) pyrimen-4-yl-1'-[(21〇-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b: 5 , 4-b']di-pyran-3,3W丨哚]-2'(1Ή)-one; 4'_(1•benzothiophen-3-yl)-l'-[(2R)-tetrahydrofuran- 2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2'(1Ή)-one ; 4'-(1-Methyl-1Η-吲哚-5-yl)-l'-[(2R)-rahydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[1] , 2 7: 5, 4 7 '] difuran-3,3,-吲哚]-2, (1 condition)-_; 4'_[3,5-bis(trifluoromethyl)phenyl H4 ( 2R),hydrofuran-2-ylhydrazino]_5,6 dihydrospiro[benzo[l,2-b: 5,4-b,]difuran-3,3,-啕哚]-2, ( 1Ή)-嗣; 4L(4-phenoxyphenyl H'-[(2R)-izghydrofuran-2-ylindenyl]-5,6-dihydrospiro [stupid [l,2-b: 5,4-b,]di-n--3,3,-吲嗓]-2,(1Ή)-one; 444-(2-mercaptopropoxy)phenyl]_r_[(2R)_® hydrogen Furan-2-ylmethyl]_5,6-dioxaspiro[benzo[l,2-b: 5,4-b,]difuran-3,3·-吲哚]-2·(1Ή)- Ketone; 4·-(4-butoxyphenyltetrahydrofuran_2_yl Indenyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-吲哚]-2'(1Ή)-one; 143924- SP-20091127-1 • 101 - 201020257 4'-(4-Methoxyphenyl)-l'-[(2R)-rahydrofuran_2_ylindenyl]_5,6-dihydrospiro [stupid [ l,2-b : 5,4-b']difuran-3,3,-吲嗓]-2,(1Ή)-one; 41-pyrimidin-5-yl-l'-[(2R)-ra Hydrogenfuran_2_ylindenyl]_5,6-dihydrospiro[{,2-b: 5,4-b']difuran-3,3,-吲哚]-2, (1Ή) -ketone; and 446-(didecylamino)>pyridin-3-yl]-indole-{[5-(trifluoromethyl)pyran-2-yl]methyl b 5,6-dihydrospiro [Benzo[l,2-b: 5,4h']di-n--3,3'-吲嗓]-2,(1,11)-one; 6'-(diphenylmethyl)-2 |,3',5,6-tetrahydrospiro [stupid [1,2 7:5,4,7]]difuran-3,8,-[1,4] dioxo-enzene [2,3 -fH哚]-7·(6Ή)-one; 3'-(4-decyloxybenzyl)-5,6-dihydrospiro[benzo[i,2-b: 5,4,7,] Furan_3'1,-,Biharindino[3,2-f]porphyrin]-2'(3Ή)-one; 2',3',5,6-tetrahydrospiro[benzo[i, 2-b : 5,4,7,] dioxin-3,8'-[1,4]dioxanthine and [2,3-f]吲哚]-7'(6Ή)-_ ; Γ -[4-(octyloxy) hen 5-[6,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran_3,3,_ρ?| 哚]-2'(1Ή)-one; 2- [3-(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran_3,3,·(9) 哚]-Γ(2Ή) -yl)propyl]-1H-iso 4 哚-1,3(2H)-dione; Γ-(3-aminopropyl)-5,6-dihydrospiro[benzo[1,2-b : 5,4-b'] 二吱 _3,3%5丨© 哚]-2'(1Ή)-ketone; Ν-[3-(2'-keto-5,6-dihydrospiro[ Benzo[l,2-b:5,4-b,]difuran·3,3,_ρ5丨嗓]_Γ(2Ή)-yl)propyl]·2-(trifluoromethoxy)benzene Guanidine; or Γ-(4-hydroxybenzyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran_3,3,_η丨嗓]_ 2' (ΓΗ)-ketone. In this particular embodiment, another specific embodiment is a compound of formula (in) wherein L is -CH2- and hydrazine is -〇-. • 102- 143924-SP-20091127-1 (S) 201020257

Example No. Compound name IC5〇5.15 1 -[(6-decyloxyacridine-:3-yl)methyl]_2,3-dihydrospiro [biting and [2,3-g][l,4] Benzodioxanthene bromide ι_ 2,(1Ή)-ketone A 5.16 (8SH'7-glycol-2-ylmethyl>2,3_dihydrospiro[吱,[2, [1' 4] benzodioxanthene _8,3% 哚], 2, (1, HV ketone AA 5.17 (8S)-1 -['2-methoxypyrimidine _5_yl)methyl] _2,3 diazane snail [biting B and [2,3-g][l,4]benzodioxanthene_8 3'-^丨嗓]_ 2,(1Ή)-ketone 5.18 (8S )-1'-Chloro-2-ylindenyl)-2,3-dihydrospiro[吱,[2,3_g] [1,4]benzodioxanthene _8,3,_吲哚]_2,(i'h)-ketone A 5.19 6-methyl-indolylpyridin-2-ylmethyl)-2,3-dihydrospiro[1,4-dioxolans[2, 3-fH 哚-8,3,- 十果]-2',7(1Ή,6Η)-dione C 5.20 4'-Fluoro-1'-{[3-(trifluoromethyl) _ base] methyl b 2,3_ dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene·8,3,_吲哚]-2' (1Ή )-ketone A 5.21 Γ-[(2,2-difluorocyclopropyl)methyl;|_2,3_dihydrospiro[吱,[2,3-g][l,4]benzodiox陆圜烯_8,3'_^ 哚]_ 2'(ΓΗ)-ketone A 5.22 Γ-甲-2,3-dihydrospiro[ olfactory [2,3_β][1,4]benzodioxanthene-8,3'-^丨哚]-2,(1Ή)-ketone A 5.23 1 '-{[4-(Trifluoromethyl)_ι,3-pyrazole·2_yl]methyl b 2,3-dihydrospiro[furo[2,3-g][l,4]benzo Dioxetine-8,3,-吲哚]-2\ΓΗ)-ketone A 5.25 9-Fluoro-fluorene-(acridine-2-ylmethyl)_2,3_dihydro-spiro[吱喃[2,3-g][l,4]benzodioxanthene _8,3'~吲哚]-2丨 (called ketone A 5.26 9-fluoro-1'-{[3- (trifluoromethyl), pyridin-2-yl]methyl}-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene-8 ,3·-吲哚]-2'(1Ή)-ketone A 5.27 9-Fluoro-indole-[(5-trans-based ρ-Bist-2-yl)methyl]-2,3-dihydrospiro[吱 并[2,3-g][l,4]benzodioxanthene-8,3'·- 丨哚 丨哚]-2·(ΓΗ)-嗣B 143924-sp-20091127-6 - 1002-

(S 201020257

Example No. Compound name 5.28 1·(ρ 比 bit-2-ylmethyl)-7,8-two-rat-6H-spiro-[pf-pyrano[2,3-g] nonene-3,3%5丨哚]-2Χ1Ή)-ketone A 5.29 1'-{[3-(Trifluoromethyl)pyridin-2-yl]methyl}-7,8-dihydro-6H-spiro[furo[2,3 -g]decene-3,3'-吲哚]-2·(1Ή)-keto B 5.31 1 decapyridin-2-ylmethyl)spiro(tetra)indole-3,3,-thieno[2,3 -f][l]benzofuran]-2(1H)-one 5,5'-dioxide C 5.32 1 -(sound bite_2_ylmercapto)_2,3_two wind snail [2,3-g][l,4] benzodioxene-8,3'-吲哚]-2·(1Ή)-ketone A 5,33 Γ-[(4,6-dimethyl Oxypyrimidin-2-yl)methyl]-2,3-dihydrospiro[吱" carboxy[2,3-g][l,4]benzodioxanthene-8,3'- <哚]-2'(1Ή)-ketone A 5.34 6-(2-decyloxyethoxy)-fluorene-(pyridin-2-ylmethyl)spiro[1·benzofuran-3,3' -啕哚]-2'(1Ή)-keto B 5.35 5-(2-decyloxyethoxy)-1·-(ρ ratio -2-ylindenyl) spirobenzofuran-3,3' -吲哚]-2·(1Ή)-ketone-------B 5.36 l'-(p-pyridin-2-ylindenyl)-2,3-dihydrospiro [bite-and-[2,3 -f][l,4] benzodioxanthene-7,3'-啕哚]-2'(1 ugly)-keto B 5.37 [-{[3-(trifluoromethyl)acridine -2-yl]indolyl 2,3-dihydrospiro[吱,[2,3-f][l,4]benzodioxene-7,3'·^丨哚]-2 ·(1Ή)-keto B 5.38 6-[(Ζ-oxo[furo[2,3-f][l,3]benzodioxene-7,3,-啕哚]-1· (2Ή)-yl) fluorenyl] oxidine-2,4(lH,3H)c _ C 6 1 -[(5-murine-l,2,4-p-plug. sit-3-yl)曱Base] snail [biting and [2,3-f][l,3]benzodioxanthene-7,3·-吲哚]-2\1Ή)-ketone A 6.1 4'-chloro- Γ-[(5-Chloro-1,2,4-soxadiazol-3-yl)methyl]spiro[V-mero[2,3-f][l,3]benzodioxanthene Alkene-7,3'-p?丨哚]-2'αΉ)-keto-1 — A 6.2 5,6-dimercapto-indole-(tetrahydro-2Η_<^-an-2-ylindenyl) snail 1_benzofuran-3,3'-throindole]-2'(1Ή)-keto B 6.3 14(3-Aceylpyrimen-2-yl)methyl] snail [ρ夫喃和[2,3 -η[ΐ,3]benzodioxanthene-7,3'-吲哚]-2·(1Ή)-ketone A 143924-sp-20091127-6 -1003- 201020257

Example No.---- Compound name-η lCs〇6.4 Γ-{[3-(2,6-diphenyl)-5-methyliso-p-Sal-4-yl] 曱美[吱喃和[ 2,3-f][l,3]benzodioxanthene-7 3,_& '哚]-2'(1Ή)-ketone' ---_ C 6.5 Γ-({2-[4 -(Trifluoromethyl)phenyl]-indole, 3-ι»塞嗤-4-yl}methyl) worm ^~~~ [吱,[2,3-f][l,3]benzo Dioxin, _7 3,-«75丨哚]-2'(1Ή)-ketone' — B 6.6 Γ-[(5-phenyl-1,3,4-p-di-2-yl-2-yl)曱 ]][螺η南和[2,3-f][l,3]benzodioxene-7,3',嗓]_ 2,(1Ή)-ketone----- B 6.7 l'-{[5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]methyl} snail [cough 0 Nanhe [2,3-f][l, 3] benzodioxolone _7,3'- cleavage]-2'(1Ή)-keto-- B 6.8 Γ-([1,3]carbazolo[4,5-b]pyridine -2-ylmethyl) snail [pf-pyrano[2,3-f][l,3]benzodioxolene-7,3'-,哚]-2'(1Ή)-one — A 7.1 Γ-[3-(Trifluoromethyl)-yl]-2,3-dihydrospiro[吱,[2,3-g] [1,4]benzodioxene-8 ,3'-吲哚]-2'(ΓΗ)-ketone A 7.2 5-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodiox Terpene-8,3'-吲哚]-1'(2Ή)-yl)methyl]methylpyrrolidinecarboxylate A 7.10 Nitrobenzyl)-2,3-dihydrospiro[吱喃和[ 2,3-g][l,3]benzoxene oxide orthoquinone]-2*(1Ή)-嗣A 7.11 Γ-(1,3-fazol-5-ylmethyl)-2, 3-Dihydrospiro[吱,[2,3-g] [1,3]benzodioxanthene-8,3·-吲哚]-2'(1Ή)-ketone A 7.12 14[5 -(trifluoromethylacridin-2-yl)methyl}-2,3-dihydrospiro[吱,[2,3-g][l,3]benzodioxolene-8, 3'-吲哚]-2,(1Ή)-ketone A 7.13 14[3-(Trifluoromethyl)acridin-2-yl]methyl}-2,3-dihydrospiro[吱吱[2 ,3-g][l,3]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one A

143924-sp-20091127-6 1〇〇4

(S 201020257

Example No. Compound name IC5〇7.14 1·-[(3-Acridine-3-ylisoxazole-5-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g] [l,3]benzodioxanthene _8,3,-吲哚]-2'(1Ή)-ketone A 7.15 (8R)-r-{[3-(trifluoromethyl) 峨 _ 2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][l,3]benzodioxene _8,3,-old 哚]-2' ( 1Ή)-keto B 7.16 Ν,Ν-dimercapto-3-[(2,-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzoic Oxygen decene _8,31_10 η^Ή)-yl)methyl]benzamine C 7.17 1 -[3-(TMFolin-4-yl)-yl]_2,3 _ Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3,_啕哚]-2'(1Ή)-ketone C 7.18 14(4- Mercapto-1,2,5-oxadiazol-3-yl)indolyl]_2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene_ 8,3·_ρ?丨哚]-2'(1Ή)-ketone A 7.19 1 _(2,3;difluorobenzyl)_2,3_dihydrospiro[吱,[2,3-g][ l,4]benzodioxanthene -8,3'-noise]-2,(1·Η)-ketone A 7.20 1 difluoro-aryl)-2,3-dihydrospiro [吱峰[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2,(1Ή)-嗣A 7.21 1 -(4-^ ))-2,3-dihydrospiro[c-buto[2 3_g][14]benzobisindene-83'-^丨嗓]-2,(1Ή)-ketone A 7.22 1 _(2_5 Benzyl)_2,3_dihydrospiro[furo[2,3-g][l,4] benzodioxanthene-8,3'-吲哚]_2, (1, HV ketone A 7.23 1 [(1rT f _'1H_benzotrienyl _5_yl)methyl]-2,3·dihydrospiro[, 味 弁 [2,3-g][l,4]benzodiox Lunene _8 3丨哚hWH)-ketone s 1 A 7.24 1 -[(3-difluorodecyloxy)octyl]_2,3_dihydrospiro [biting nucleus U,4] benzodioxane陆园稀_8,3,一丨哚A 7.25 1 -[(2-Fluoro-6-trifluoromethyl)benzyl, 2'(1Ή)-one A 143924-sp-20091127-6 -1005- 201020257

Example No. Compound name ic5〇7.26 1 _[(ϋ气曱基芹)_2,3-Dihydrospiro[吱喃-g][l,4]Oxylene dioxane 丨哚]_2,( ι,η)_ A 7.27 1 -[(2ή二21oxy)-character]·2,3·dihydrospiro[,,[2,3-g] U,4] stupid and dioxane _8,3'-吲嗓]_2,(i,h)-ketone A 7.28 1 -[2-(2,2,5-Dimethyl_ι,3_dioxoindole_2_yl)B Base]_2 3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene'·8,3ι_ 啕哚]-2'(1Ή)-ketone A 8 l '-[(2S)-l,4-Dioxaindole_2_ylmethyl] snail [吱,[2,3_Ώ [1,3] benzodioxanthene _7,3·-吲嗓]_2,(ι,η)-ketone A 8.1 7'-gas^-1'-[(2 ft)-tetrahydrofuran_2_ylindenyl]_5,6-dihydrospiro[benzo[l,2 -b : 5,4-b']difuran-3,3,-吲哚]-2,(1Ή)-keto B 8.2 7'-fluorohand tetrahydrofuran_2_ylindenyl]_5,6-dihydrogen Snail [benzo[l,2-b:5,4-b']dioxan-3,3'-吲哚]-2,(1Ή)-ketone A 8.3 4'-fluoro-7'-A Base-r-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3 ,- 哚 哚]-2'(1Ή)-ketone A 8.4 1L pentyl-2,3-dihydrospiro And [2,3-g][l,4]benzodioxanthene-8,3'-"5| 哚]-2'(1Ή)-ketone A 8.5 (8R)-1'-[( 2R)-1,4-dioxoindolin-2-ylindenyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3·-吲哚]-2'(1Ή)-keto C 8.6 (81〇-1'-[(25)-1,4-dioxoindole-2-ylindenyl]-2,3- Dihydrospiro[Nitrate[2,3^][1,4]benzodioxanthene-8,3'-«*丨哚丨哚]-2Χ1Ή)-ketone C 8.7 (8SH'-[( 2S)-1,4-Dioxindolin-2-ylmethyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3'-thirty 哚]-2'(1Ή)-ketone A 8.8 (8S)-r-[(2R)-l,4-dioxolybden-2-ylindenyl]-2,3-di Hydrogen snail [吱,[2,3-g][l,4]benzodioxanthene-8,3'-蚓哚]-2'(1Ή)-ketone A 143924-sp-20091127-6 -1006- 201020257

Example No. Compound name ic5〇8.9 1 -[(211)-tetrahydrofuran-2-ylmethyl]_6,7-dihydrospiro[benzo[l,2-b. 4,5-b']dioxan_ 3,3'-吲嗓]_2,(i,h)-keto B 8.10 1 -[(2R)-1,4-oxoindol-2-ylindenyl]_6,7-dihydrospiro"舁[l,2-b . 4,5-b']二吱喃-3,3·-«»5丨嗓ι_2'(ι'Ην®§) B 8.11 1 Methyl j_3,4·Dihydro _ _ _ 螺 [吱 开 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ 1,4-monooxanthene-2-ylindenyl]_3,4-dihydro-2H_spiro[吱,[2,3-h][l,5]benzodiazepineseptene] 9 3,_吲哚]-2'(1Ή)-ketone B 8.14 3-methyl_14__tetrahydrofuran_2_yl)indenyl)_2Η snail [benzopyrene 0 Nanhe [6,5-^ 嗤-7,3'-dihydroindole]-2,2,(3Η,6Η)-C 8.15 7'-Fluoro-1·-〇 咬-2-ylmethyl)-3,7-II Hydrogen-2Η-spiro[benzofuro[5,6-b][l,4]dioxolysene_8,3,-dihydroindole]-2'-one A 8.16 7'-fluoro group -Γ-((3-(Trifluoromethyl oxaridinyl-2-yl)indolyl)_3,7-dihydro-2-indole-spiro[benzofuro[5,6_b][1,4]dioxene 'Cerene-8,3'-dihydrorhadyl]-2'-keto A 8.17 3 -[2-( Fluoromethyl)-based]-2,3-dihydrospiro[啥,[2,3-g][1,4]benzodioxolene-8,Γ-茚]-2, (3 ,H)-keto A 8.18 14(5-fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[,1,3-g][l,4]benzodiox Luyuan _8,3ι_吲哚]_ 2,(1Ή)-ketone A 8.19 (8S)-1 -[(5-fluoro ruthenium ratio β定_3_基)methyl]_2,3_二Hydrogen snail [bito-[2,3-g][l,4]benzodioxanthene_8,3,_吲哚]_ 2'(ΓΗ)-ketone A 9 3-methyl-1 -{[5-(Difluoroindolyl) oxime-2-yl] fluorenyl} 嗔 嗔 and [3,2-f][l,2] benzopyrene 嗤-5,3' -»5丨嗓]-2,(1Ή)-ketone A 9.1 Γ-[2-(2-methoxyethoxy)ethyl]_5,6-dihydrospiro[benzo[l,2-b : 5,4-b']difuran_3,3,-峋哚]-2,(1Ή)-keto B 143924-sp-20091127-6 -1007 - 201020257

Example No. Compound name IC5〇9.2 l'-{[(2S)-5-ketotetrahydropyrrol-2-yl]methyl}-5,6-dihydrospiro[benzo[l,2-b: 5 ,4-b,]difuran-3,3'-indole]-2'(1Ή)-keto C 9.3 Γ-[2-(^-keto-l,3-tetrahydrocarbazol-3-yl) Ethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-indole]-2,(1Ή)-one C 9.4 Γ -(4-pyridin-2-ylindenyl)-5,6-dihydrospiro[benzo[1,2-b : 5,4-b,]difuran-3,3'-啕哚]-2 '(1ah)-keto B 9.5 Γ-(mouth-2-ylindenyl)-5,6-dihydrospiro[benzo[i,2-b : 5,4-b,] difuran-3 ,3'-啕哚]-2'(1Ή)-ketone A 9.6 Γ-(pyridin-4-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b : 5,4 -b,] difuran-3,3'-吲哚]-2·(1Ή)-ketone A 9.7 Γ-0 ratio ρ well-2-ylmethyl)-5,6-dihydrospiro[benzo[ 1,2 7:5,4-b,] Difuran-3,3'-indole]-2'(1Ή)-ketone A 9.8 1'-[0-fluoro-1-benzofuran-2-yl ) 曱 ]]_5,6_2 argon snail [benzo[l,2-b: 5,47'] dis-methane-3,3'-吲嗓i_2' (THV net A 9.9 1 -0 ploughing -3-ylindenyl)-5,6-dihydrospiro[stuppy p, 2:7,5,4-b,] 吱 吱-3,3W 卜 朵]-2'(1Ή)-ketone B 9.10 14(2-keto-1,3- Hydroxazole _5_yl) fluorenyl iι_5 6_-hydrospiro [benzo D, 2-b ·· 5,4 bisdifuran _3,3,j 哚] 2,& 1 ketone C 9.11 1 - [3-(Alkoxy- octosyl)-5,6-dihydrospiro [Benzene like seven: 5 4 VII,] Dipyran-3,3·-吲哚]-2·(1Ή)-keto B 9.12 14(1·^ f _1Η_benzimidazolyl)methyl]-5,6-dihydrospiro[本和[l,2-b . 5,4七']二吱喃_3,3U5丨哚ι_2,(ι,η)_ketone B 9.13 1 and triazole-2-ylmethyl)-5,6-dihydrospiro[benzo[,2,7,5,4,7]didentate _3, 3'-吲嗓ι_2'ΠΉν西网A 9.14 2-[(2-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3'3' -吲哚]-Γ(2Ή)-yl) fluorenyl] methyl benzoate A 9.15 3-[(2-keto-5,6-dihydrospiro[benzone to: 5 4 -7] difuran -3,3'-W哚]-1'(2Ή)-yl)methyl]benzoic acid methyl ester A 9.16 4-[(2'-keto-5,6-dihydrospiro [stupid [u_b: 5 4 VII,]difuran-3,3 丨哚]-1'(2Ή)-yl)methyl] methyl benzoate A 143924-sp-20091127-6 -1008- 201020257

Example No. Compound name IC5〇9.17 Narrow oxy)propyl]-5,6-dihydrospiro[benzo[12_b : 5,4_b,] difuran-3,3·-峋哚]-2' (1Ή> Ketone B 9.18 5·-fluoro^-1,4(2R)-tetrahydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran _3,3,-sideside]-2,(1Ή)-keto B 9.19 6'-fluoro^-r-[(2R),hydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzene And [l,2-b: 5,47'] bismuth _3,3'-吲哚]-2'(1Ή)-keto B 9.20 Γ-[2-(2-methoxyethoxy) Ethyl]_2,3_dihydrospiro [bito-and-[2,3-name][1,4]benzodioxanthene _8,3,_啕嗓]_ 2ΧΓΗ)-ketone A 9.21 2-mercapto-1·-(ν-pyridin-2-ylindenyl) snail jv-mero[2,3_耶,3]benzoxazole-7,3'-啕哚]-2| 1Ή> Ketone C 9.22 1·-[(5-Alkyl-1-methyl-1Η-amido-2-yl)methyl]_2·indolyl snail [Blowing and [2,3-f][l , 3] benzopyrazole-7,3,-吲哚]-2'(ΓΗ)-keto C 9.23 4-mercapto-1'-(((11)-tetrahydrofuran-2-yl)indenyl)_4 , 7-dihydrospiro [stupid and biting and [5,6-b][l,4] 吟耕-8,3,-dihydro 嗓]-2,,3(2H)-dione A 9.24 3-methyl-indole-indolepyridin-2-ylmethyl) snail Oxazole-5,3'-吲哚]-2'(1Ή)-嗣A 9.25 3-mercapto-purine-(ρ-pyridin-3-ylmethyl) snail [吱 并, p, 2-f] [l,2]benzoxazole-5,吲哚]-2·(1Ή)-ketone A 9.26 3-mercapto-1'-[(2R)-iz9hydrofuran-2-ylmethyl] snail [Cough and [3,2-f][l,2]benziso, No. 5,3·-吲嗓]-2'(1Ή)-keto B 9.27 5,6-Dimethyl-oxime -(tetrahydro-2Η-«的痕-4-ylmethyl) snail [ι_笨和furan-3,3'-吲哚]-2'(1Ή)-ketone C 9.28 5,6-didecyl -Γ-(pyridin-2-ylmethyl)spiro[1-benzofuran_3,3,_啕哚]-2'(1Ή)-one' B 9.29 5-fluoro-6-methoxy- Γ-(tetrahydro-2Η-ρ底- -4-ylmethyl)spiro[1-benzofuran-3,3'-吲哚]-2'(1Ή)-one C 9.30 5-fluoro-6 -decyloxy-1·-{[5-(trifluoromethyl)p-pentan-2-yl]methyl}spiro[1-benzofuran-3,3W丨哚]-2'(1Ή)- Ketone B 143924-sp-20091127-6 -1009- 201020257

Example No. Compound name IC5〇9.31 5,6-Difluoro-Γ-(ρ is more than 曱-3-ylindenyl) snail [1-Benzene bite 0 South-3,3^51 哚]-2'(1Ή) -keto C 9.32 5,6-difluoro-l'-{[5-(trifluoromethyl)pyran-2-yl]methyl}spiro[1-benzofuran-3,3'-吲哚] -Τ(ΓΗ)-ketone C 9.33 6-Methoxy-l'-indolepyridin-2-ylindenyl)·2Η-spiro [benzofuran-3,3'-diazaindole]-2* -Net A 9.34 6-Methoxy-indole-0-pyridin-3-ylmethyl)spiro[1-benzofuran-3,3·-啕哚]-2'(1Ή)-ketone A 9.35 6- Methoxy-oxime-(tetrahydro-2Η-喊冰冰曱基)spiro[1-benzofuran-3,3'-啕哚]-2'(1)-keto B 9.36 6-oxime Γ-Γ-(tetrahydro-2Η-mum-2-ylindenyl)spiro[1-benzofuran-3,3'-啕哚]-2'(1Ή), A 9.37 benzyloxy)hanyl ]-2,3-di-spiro[吱,[2,3-g][l,4] benzodioxanthene-8,3'-吲哚]-2'(ΓΗ)-keto B 9.38 Γ-[4-(Benzyloxy)-yl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3M丨哚]-2 '(ΓΗ> Ketone B 9.39 (8S)-r-[4-(benzyl,oxy)ykyl]-2,3-dihydrospiro[吱,[2,3-g] [1,4]benzene And dioxane terpene 丨哚]-2'(1Ή)-keto B 9.40 {5-[(2·-ketone) Base-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-1,(2Ή)-yl) Methyl>pyridin-2-yl}aminocarbamic acid tert-butyl ester B 9.41 3-曱-Γ-[2-(trifluoromethyl) aryl] snail [3, 2 rhyme 12 Benzoiso-p-azole-5,3'-吲哚]-2'(1Ή)-keto B 9.42 3-mercapto-1'-{[3-(trifluoromethyl)acridin-2-yl ]曱基} snail[吱,[3,2-f][l,2]benzoisoxazole_5,3,-吲哚]-2,(1Ή)-keto B 9.43 1,_[3U Oxy]propyl]-2,3_dihydrospiro[吱,[2,3_g][l,4] benzodioxanthene-8,3,-吲哚]-2'(1Ή) -ketone A 9.44 (2·-keto-2,3-dihydrospiro [bito-and-[2,3-g][i,4]benzodioxanthene-8,3,-吲哚] -i,(2'H)-yl)ethyl acetate A 143924-sp-20091127-6 -1010- 201020257

Example No. Compound name ic5〇9.45 i -U(4;^2,2-dimethyl_U_dioxoidene) methyl} 2 3_ : wind snail [吱, 并[2,3-phan [ 1,4] benzodioxanthene-8,3-吲哚]_2'(1丨印_ketone A 9.46 6_methyloxycarbonyl)-2,-ketodihydrospiro[1- Benzofuran_3,3,_吲哚]_5_carbonitrile B 9.47 6-methoxy-2'-keto-1, _(pyridine_2_ylmethyl)_Γ, 2,_dihydrospiro [1-benzofuran_3,3,_吲哚]_5_carbonitrile, C 9.48 6-1 ^ -2'' base·ι'_(ρ-pyridine-2-ylmethyl)_Γ, 2ι二Hydrogen snail and furan-3,3,-吲哚]-5-carbonitrile C 9.50 6-fluoro-2'-keto_1'-(; 2-(trifluoromethyl)-yl]-r, 2,_Dihydrospiro[1-benzofuran_3,3'-吲哚]_5-carbonitrile C 9.51 6_Fluorin: 2'-,yl-l'-{[3_(trifluoromethyl) Pyridine_2_yl]methyl)_dihydrospiro[ι_笨和furan_3,3,_吲哚]_5carbonitrile C 9.53 3-[(2'-keto-2,3-dihydrospiro)卜失乌南[2,3-g][l,4]benzodioxanthene-8,3,,哚Η'(2Ή)-yl)methyl]benzoic acid methyl ester A 9.54 Γ- [2-(2-methoxyethoxy)ethyl]_3·methyl snail [biting mers [3,2_f][l'2] benzopyrene _5, 3·-ρ5卜多]-2'(1Ή)-keto B 9.55 3-mercapto-fluorenyl-(3-mercaptobutyl)spirobam[3 2_illus [12] benzisoxazole -5,3·-啕哚]-2,(1Ή)-_ A 9.56 曱手-Γ-01 than tilling-!2-ylmethyl;) snail [ρ失喃[3,2-f][ i,2]benzisoxazole-5,3·-吲哚]-2,(1Ή)-ketone A 9.57 Γ-[(3-fluoropyridin-2-yl)indolyl]-3-fluorenyl Snail [furo[3,2-phantom [1,2] benziso 4 sal _5,3'-吲哚]_2, (1 ugly)-keto B 9.58 2-[(3-mercapto-2' - Oxytropy [吱 benzo benzoisoxazole-5,3 卜木]-1 (2Ή)-yl) fluorenyl]-ΐ, 3-«» 唾-4-carboxylic acid vinegar B 9.59 4- [(2'-keto-2,3-dihydrospiro[Vf-[2,3-g][l,4]benzodioxanthene-8,3'-W哚]_γ( 2Ή)-yl)mercapto]methyl benzoate A 9.60 Γ-[(4-mercapto-oxalin-2-yl)indenyl]_2,3-dihydrospiro[吱,[2,3- g][l,4] stupid and dioxane decene _8 3, 丨哚 2, (1 Ή)-ketone B 143924-sp-20091127-6 • 1011- 201020257 In this embodiment A, one A specific example is a compound of formula (III) selected from the group consisting of: Γ-0-pyridin-2-ylmethyl)-6,7-dihydrospiro[benzo[nb:4,5-b,]difuran-3,34哚]-2'(ΓΗ)-ketone; l'-[(2R)- E3 Hydrofuran-2-ylmethyl]_6,7-dihydrospiro[benzox,2-b: 4,5-b']dipyran-3,3.5丨哚]-2(1Ή) -ketone; or 1'-[(211)-1,4-dioxolyl-2-ylmethyl]-6,7-dihydrospiro[benzo[i,2-b: 4,5-b ,] Difuran-3,3'-吲哚]-2·(1Ή)-one. Another embodiment of the invention is a compound of formula (IV) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is a compound of the formula αν), wherein each R8 is independently hydrogen, hydroxy, bromo, carbyl, cyano, fluoro, fluorenyl, difluoroethenyl, Alkoxy, μmethylethoxy, 2methoxyethoxy, benzyloxy, fluorene tert-butoxycarbonyl) tetrahydropyrrole! Alkoxy group, tetrahydropyridyl 3-yloxy group, amine group, fluorenylamino group, methyl arylamino group, [(t-butoxycarbonyl)tetrahydropyrrol-3-yl]amino group, 6 _Methoxypyridine, 孓methyl-1,2,4-oxadiazole, amino (imido)methyl or (tetrahydropyrrole-based base. ' In this implementation In another embodiment, a specific embodiment is a compound of formula (IV) wherein two R8 groups are taken together with the adjacent carbon to which they are attached to form a fused dioxoenyl ring, fused oxime An acyl ring, a fused u-diketothiophene ring, a fused u, a 5-oxadiazolyl ring, a fused tetrahydropyranyl ring, a fused 2,3_2 a hydrogen pyridinyl ring, a fused & fluorenyl-4,5-dihydroisoxazolyl ring or a conjugated pyridyl ring, and the remaining W group, 143924-SP-20091127-1 - 103- 201020257

Example No. Compound name IC5〇9.64 5,6--gas ratio 淀-2-ylmethyl) snail [1_benzoxanthene J 3, (4) 哚]-2'(ΓΗ)-ketone' B 9.65 5, 6-Difluoro-1'-(tetrahydro-2-indole-'m--4-ylmethyl) snail_benzopyran-3,3'-啕哚]-2'(1Ή)-ketone C 9.66 2-[3-(2·-keto-5,6-dihydrospiro[benzo[i,2-b : 5 4-b,] - ρ fuchuan-3,3,-(f)哚]-1 ,(2Ή)-yl)propylHH-iso^丨嗓_"73(2h) diketone, A 9.67 1'-{[5-(yloxy)p than bit-2-yl]methyl} Spiro[p-f-[3,2-e][2,l,3]benzo-dipyridinium-2,(1Ή)-keto B 9.70 (8S)-142-(2-methoxy B Oxy))^^[2,3-g][l,4]benzodioxanthene_8 3,·ρ?| 哚]-2ΧΓΗ)-ketone' A 9.71 6'-[2 -(2-methoxyethoxy)ethyl]·2,3-dihydrospiro[吱嗔,[2,3-g][l,4]benzodioxene terpene Oxazo[5,4-eH 哚]-7'(6Ή)-keto B 9.72 b-Ο1pyridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g ][l,4] Bentodioxene terpenes-8,8'-[l,3>seda[5,4-e]4丨哚]-7'(6Ή)-keto B 9.73 4' ,6'-dimethoxy-142-(2-methoxyethoxy)B ]_2 3_Dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene_8,3,_吲哚]-2'(1Ή)-ketone C 9.74 4 ',6'-Dimethoxy-indole-indole ratio bite 2-ylmethyl)_2,3_dihydrospich-[2,3-g][l,4]benzodioxan Terpene _8,3,-啕哚]-2'(ΓΗ)-ketone B 9.75 6-(2-methoxyethoxy)-142-(2-methoxyethoxy)ethyl] snail [1-benzofuran-3,3'-throindole]-2,(1Ή)-one B 9.76 M2-methoxyethoxy)-l'-[2-(2-foxyethoxy) Ethyl] spiro[1-benzofuran-3,3'-吲哚]-2,(1Ή)-keto B 10 1-(嗒耕-4-ylindenyl)-5,6-dihydrospiro [Benzo[i,2-b : 5,4-b,]difuran-3,3W丨哚]-2'(1Ή)-one B 11 chloro-1,3-pyrazol-5-yl) Methyl]spiro[furo[2,3_f][1,3]benzodioxolene-7,3'-吲哚]-2'(1Ή)-ketone A 143924-sp-20091127-6 - 1012- (s 201020257

Example No. Compound name ic5〇11.1 {[2(-Methylamino)-i,3-P-pyrazole-5-yl]methyl}Spiro[2,3-£][1,3]Benzene Oxygen urethene _7,3, _ 吲 2'(1Ή)-ketone JA 11.2 1 [(2-muffol-4-yl-1,3-p-conazole-5-yl)methyl] snail [吱其[2,3-f][l,3]benzodioxanthene 嗓1 2,(1Ή> ketone J-B 11.3 1 _[(2: hexazone-1-yl-U_ Thiazole _5_yl) and [2,3-f][l,3]benzodioxolene oxime 1 2'(1Ή)-ketone J_ B 11.4 1 -[(2-methoxy- 1,3-pyrazol-5-yl)methyl] snail [吱 并 「 2 2 [1,3] 并 dioxin _7,3'-p?丨嗓]-2' (ΓΗ ), A 11.5 Η hexahydropyridin-4-ylmethyl)-5,6-dihydrospiro-5,4-b1]difuran-3,3·-Η丨哚]-2'(1Ή>ketone' C 11.6 1-{[1-(1-decylethyl)hexahydropyridine 4-yl]methyl b 56-snail [benzo[1,2-7:5,4-7,]difuran_3 ,3,_一风2,(1Ή)-keto C 11.8 1 -[(1-ethylhexahydropyridin-4-yl)methyl]_5,6-dihydrospiro[benzo[l,2-b : 5,4-b']二吱嗔_3,3'-port noise extraction]-2'(1Ή)_ketone C 11.10 1 -[(1-mercapto six gas ρ than bit-4-yl)曱Dihydrospiro[benzo[l,2-b: 5,4- b'] 二吱味-3,3'-4卜朵]_2'(1Ή)-嗣D 11.12 3-[(2-3⁄43⁄4 base-5,6-one snail [benzo[l,2-b] : 5,47'] Di-pyran-3,吲哚]-Γ(2Ή)-yl)methyl]benzoic acid C 11.13 Γ-{4-[5-(trifluoromethyl)-1,2, 4-oxadiazol-3-yl]]}},6-diphos snail [benzo[l,2-b: 5,4-b'] diterpene _3,3,_吲味] -2,(1Ή)-keto B 11.14 Γ-[4-(^·methyl-1,2,4-«diazol-3-yl];]_5,6-dihydrospiro[benzo[ l,2-b : 5,4-b']difuran-3,3,-呻哚]-2'(1Ή)-ketone A 11.15 Γ-[(5-pyridin-4-ylfuran-2-yl) )methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-^丨哚]-2, (1Ή>ketone B 11.16 1·-(4-Pyridin-3-ylbenzyl)-5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]difuran-3,3'-峋哚] -2'(1'11)-keto B 143924-sp-20091127-6 •1013- 201020257

Example No. Compound name ICso 11.17 Γ-[(2'-Fluorobiphenyl-4-yl)indolyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Dioxin-3,3,-叼丨嗓]-2,(1Ή)-keto B 11.18 Γ-{2-[5-(Trifluoromethyl)-1,2,4-oxadiazol-3- Ethyl}ethyl}spiro[吱1 喃[2,3-f][l,3]benzodioxolene-7,3,-啕哚]-2'(1Ή)-ketone A 11.19 4 '-Gas-anthracene-{[5-(trifluoromethyl)-1,2,4′′dis-s--3-yl]methyl} snail [ρ夫喃和[2,3-f][l , 3] benzodioxanthene _7,3, 丨哚 丨哚]-Τ(ΓΗ)-ketone A 11.20 4'-gas-anthracene-[(5-cyclopropyl-1,2,4- No. 11 dioxin-3-yl) fluorenyl] snail [吱,[2,3-f][l,3]benzodioxanthene _7,3,-< 哚]-2ΧΓΗ)- Ketone A 11.21 4'-Gasyl-1'-{1-[5-(difluoroindolyl)-1,2,4′′dis-s--3-yl]ethyl}spiro[2,3 -f][l,3]benzodioxanthene_7 3,·吲哚]-2'(1Ή)-ketone A 11.22 Γ-{[5-(difluoromethyl)-1,2, 4"diazol-3-yl]fluorenyl}spiro[2,3-f][l,3]benzodioxolene-7,3,_啕哚]-2' (ΓΗ )-ketone A 11.23 Γ-[(5-Third-butyl-l,2,4-oxadiazol-3-yl)methyl] snail [吱,[2,3-f ][l,3]benzodioxolene-7,3'-吲哚]_ 2,(1Ή)-ketone A 11.24 l'-[(5-cyclopropyl-1,2,4′′ Diazol-3-yl)indolyl] snail [吱,[2,3-;〇[1,3]benzodioxolene-7,3. 5丨哚]-2'(1Ή)- A 11.25 4'-Chloro-1·-{[5-(1-mercaptoethyl)-indole, 2,4-oxadiazol-3-yl]methyl} snail [吱和[2,3 -f][l,3]benzodioxanthene _7,3'_ 哚 哚]-2(1Ή)-ketone A 11.26 1L{[5-(1-methylethyl)-1,2 , 4-oxadiazol-3-yl]methyl} snail [furan P,3-f][l,3]benzodioxolene-7,3,-吲哚]-2, (1Ή )-ketone A 11.27 143-(5-methyl-1,2,4′′diazol-3-yl)-yl]-5,6-dihydrospiro[benzo[l,2-b: 5, 4-b']difuran-3,3,- sorghum]-2'(1Ή)-ketone A 143924-sp-20091127-6 •1014- 201020257

Example No. Compound name 11.28 1'-{3-[5-(Trifluoromethyl)-1,2,4′′diazol-3-yl] benzyl bromide 5,6-dimer snail [benzo[l ,2-b : 5,4-b'] 二 p夫味_3 3,-口弓1 哚]-2'(1Ή)-ketone' 11.29 Γ-[4-(^ base-4Η-1,2 , 4-triazol-3-yl)benzyl]_5 6_dioxaspiro[benzo[l,2-b:5,4?']difuran_3,3'-(9)哚l-2, ( Tm-嗣11.30 2-[(2'-keto-5,6-dihydrospiro[{-[B][U_b: 5 4-7]]difuran-3,3'-吲哚]-Γ(2Ή)-yl )methyl]benzoic acid 11.31 4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-b,]dioxan-3,3'- <哚]-Γ(2Ή)-yl) fluorenyl]benzoic acid 11.32 5-[(2-_yl-2,3-di-spiro[p,pyrano[2,3_g][i,4]benzene Dioxetemene-8,34哚]-l,(2,H)-yl)methyl]anthracene acid 11.33 11.34 11.35 11.37 11.39 11.41 11.42 Ν,Ν-dimethyl,-5-[ (2·-keto-2,3-dihydrospiro[2,3_g][Μ]benzodioxanthene_8,3·,丨哚]-ΐ,(2Ή)-yl )methyl]furan-2-carboxyindole Γ-(3-hydroxypropyl)-5,6-dihydrospiro[benzo(10)7:5,4-7,]difuran-3,3'-啕哚]-2·(ΓΗ>-keto 2'-keto-l'-[, (2R) - tetrahydro-squeaking _2_based f Η,, 2,, 5 6 four - snail [benzo[l,2-b: 5,4 seven'] two biting -33% bow 丨嗓]_4· -carbonitrile 4'-[(dimethylamine#yl)methyl]-i'_[(2R)-tetrahydrofuran-2-ylmethyl]_ 5,6-diterpenoid [benzo[1,2-7 :5,4-b']二咬喃-3 3Ί 哚]-2'(1Ή)-®Ι ' 4-(tetrakis ρ than 嘻-1-ylmethyl)_1'_[(2) tetrahydrogen吱 _2 _ _ _ _ _ _ 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 '-Amine^-,1'-[(2R)-e3hydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[l,2-b:5,4,7,]difuran- 3,3,-啕哚]-2,(1 H), 1 -[(4-methylmorphine-2-yl)methyl]-5,6-dihydrospiro[benzo[l,2 -b,5,4-b1]二吱叫-3,3,-叼卜朵]-2*(1 Ή)-ketone 1 methylethyl)folinin-2-yl]methyl}-5 ,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-啕哚]-2·(1Ή),

143924-sp-20091127-6 •1015· 201020257 Example number -------τ Compound name----- ic5〇11.43 1 -Methyl-5,6-one snail [Benzo[l,2- b : 5,4-b'] two p. South-3 3, 吲哚]-2'(1Ή)-ketone' .---- B 11.44 Γ-[4-(1Η-tetrazol-5-yl)octyl]-5,6-dihydrospiro [Benzo[1,27^^--C 11.45 (3-hydroxyindolyl)-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran- 3,3,-♦Duo]-2,(1Ή)-keto B 11.46 Γ-(4-isofolin-4-ylindenyl)-5,6-dihydrospiro[benzo[i,2-b : 5,4-b']difuran-3,3'-吲哚]-oxime)-one - B 11.47 6-Amino-1 -[(21〇-tetrahydrofuran_2_ylindenyl] snail [! _benzofuran-3,3'-啕哚]-2·(1Ή)-keto C 11.48 Ν-{2'-keto-l'-[(2R)-rahydrofuran-2-ylmethyl] -Iso-spiro[1-benzofuran-3,3'-H丨哚]-6-yl}nonanesulfonamide---- C 11.49 6-hydroxy-indole-(3-methylbutyl Snail [i_benzofuran_3,3,_^丨哚^·'-2,(1Ή)-ketone-------A 11.50 6-hydroxy-indole-(3-mercaptobutyl) _5-(Trifluoroacetamido) spirofl_furfuran-3,3'-吲哚]-2'(1Ή)-ketone----- C 11.52 6-[(3R)-ra Hydropyrrole-3 -ylamino]-1,-{[5-(trifluoromethyl) olyl-2-yl] fluorenyl} snail [1, benzopyrano-3,3,_P 丨哚]-2 '(1Ή)-keto_-B 11.53 6-Hydroxy-r-[(2R)-nghydrofuran_2-ylindenyl]spiro Q•benzopyrene~ -3-3,吲哚]-2'(1 ketone-ketone B 11.54 6-(1-mercaptoethoxy)-i'-[(2R),hydrofuran-2-ylindenyl][1-benzene吱"South-3,3'-H丨嗓]-2·(1Ή)----B 11.56 6-[(3S)-tetrahydropyrrol-3-yloxy]-1,_[ (2 feet)-tetrahydrofuran_2·ylmethyl]spiro[1-benzo-bite-flavor-3,3'-^丨口朵]-2'(1Ή)-keto-androstate 1 C 11.58 6-[( 3R)-tetrahydropyrrol-3-yloxy]-1,-[(211)-tetrahydrofuran_2_ylindenyl]spiro[1-benzopyrifin-3,3'-τ»5丨 beer] -2'(ΓΗ)-_hydrochloride C 11.60 l'-[(2R)-rahydrofuran-2-ylindenyl]spiro[benzo[nb ··5,4-b,] difuran-3 , 3M Budu]-2·,5(1Ή,6Η)-dione B 143924-sp-20091127-6 -1016 -

(S 201020257

Example No. Compound name IC5〇11.61 1 _(tetrahydroindol-3-ylmethyl)-5,6-dihydrospiro[benzo with 2 b : 5,4-b']difuran-3,3' -吲哚]-2ΧΓΗ)-ketone C 11.62 N-(l-methylethyl)-3-[(2·-mercapto-5,6-dihydrospiro[benzo[2]b: 5,4-7' ] 吱%-3,3,_十朵Η,(2Ή>yl)methyl]tetra-pyrrole-1-carboxamide C 11.63 1 -[(4-methylhexahydro-p ratio ρ井_ι_ Methyl] snail [ρ 喃 〇 〇 [1,3] benzodioxanthene -7,3'-吲嗓]_2'(1Ή)-ketohydrochloride A 11.64 (3S)- 6-decyloxy-5-methyl-l'-[(4-methylhexahydropyrazine)methyl]spiro[1-benzopyrene-3,3'-p 嗓]-2 ,(1Ή)-ketohydrochloride A 11.65 (3R)-6-methoxy-5-methyl-indole-[(4-methylhexahydropyrryl) fluorenyl] spiro[1-benzofuran -3,3'-吲哚]-2'(1Ή)-ketohydrochloride B 11.66 (3S)-1'-[(2R)-Tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro [Benzo[l,2-b:5,4-b']difuran-3,3,-吲哚]-2,(1Ή)-one A 11.67 (3R)-l'-[(2R)- Ra hydrogen ρ, chloro-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2 ,(1Ή)-ketone C 11.68 (3R)-1'-[(2S)-tetrahydrofuran-2- Methyl]-5,6-dioxaspiro[benzo[l,2-b:5^-b,]difuran-3,3,-啕哚]-2·(1Ή)-one A 11.69 (3S )-1'-[(2S)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3' -啕哚]-2"(ΓΗ)-ketone C 11.70 r-{[(2S)-l-methyl-5-ketotetrahydropyrrol-2-yl]methyl}-5,6-dihydrospiro [Benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2'(1Ή> Ketone C 11.71 l'-[(3-mercapto-2-one) -1,3-tetrahydrocarbazol-5-yl)indolyl] snail [snolo[2,3-f][l,3]benzodioxol-7,3·-峋哚]-2\1Ή)-ketone C 11.72 Γ-{[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl} snail [吱 并[2,3- f][l,3]benzodioxanthene-7,3·-啕哚]-2'(ΓΗ)-ketone A 143924-sp-20091127-6 -1017- 201020257 Instance No. -- Compound Name ^ 5〇11.73 Ν-Isopropyl-3-[2-(2·-oxaspiro[pf-pyrano[2,3-f][l,3]benzodioxene-7,3'-哚]]-1'(2Ή)-yl)ethyl]hexahydropyridine-1-carboxyguanamine----- Β 11.74 5-[(2'-oxaspiro[furo[2,3-f]] [l,3]benzodioxanthene^7 吲哚]-1'(2Ή)-yl)methyl]P-thiophene-3-carbonitrile' —-- -- A 11.75 2 keto-anthracene, 2'-dihydrospiro [bito-and-[2,3-f][l,3]benzodioxene-7,3'-啕哚]-7' -曱nitrile---- B 11.78 3'-[(3-Mosylpyridin-2-yl)indolyl]-2,3-dihydrospiro [V-dea-[2,3-g][l , 4] benzodioxanthene dilute-8, Γ-茚]-2'(3Ή)-_ A 11.79 3'-{[3-(methyl aryl) ρ than -2-yl]methyl }-2,3-Dihydrospiro@~~ mer to [2,3-g][l,4]benzodioxanthene-8, Γ-茚]_ 2,(3Ή)-ketone-- --- Β 11.80 2-[(2'-keto-2,2',3,3·-tetrahydrospiro[c-buto[2,3-g][l,4]benzodioxanthene] Alkene-8,1·-茚]-3·-yl)methyl]pyridine-3-carbonitrile A 11.81 (83)-1'-{[3-(difluoromethyl) ρ than bit-2-yl ]曱基}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3'-吲' 哚]-2' (ΓΗ )-ketone A 11.83 Γ-[3-(5-mercapto-1,2,4-<» No.2"--3-yl)-yl]-2,3-dihydrospiro [biting and argon [ 2,3-g][l,4]benzodioxanthene _8,3'-吲哚]-2'(1Ή)-ketone A 11.84 Γ-[4-(5-mercapto-1, 2,4-p-di-n--3-yl)-yl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3 '-啕哚]-2'(ΓΗ)-ketone A 11.85 6-(5-methyl- 1,2,4-p-di-n--3-yl)-1'-indole-But-2-ylindolyl) spiro [1-benzofuran-3,3.哚]]-2Χ1Ή)-ketone" B 11.86 3-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene] Alkenyl-8,3'-啕哚Η'(2Ή)-yl)methyl]benzoic acid C 11.87 4-[(2'-keto-2,3-dihydrospiro[[,3,3 ^][1,4]benzodioxanthene-8,3'-吲哚]-Γ(2Ή)-yl)indenyl]benzoic acid C 11.90 1,-{[5-(trifluoromethyl )-1,2,4-oxadiazol-3-yl]methyl}_2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene哚]-2'(1Ή)-ketone A 143924-sp-20091127-6 -1018-

(S 201020257

Example No. Compound name IC5〇11.92 trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}-2,3-dihydrospiro [bito-and-[2,3-g][ 1,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-ketone A 11.94 Ν-{3-[(2'-keto-2,3-dihydrospiro) [ρ失失和[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-Γ(2Ή)-yl)methyl]phenyl}methanesulfonate Amine B 11.95 14(1-Iso-pyridin-2-yl)indenyl]-2,3-dihydrospiro[吱,[2,3-叾][1,4]benzodioxanthene-8 ,3'-吲哚]-2Χ1Ή)-keto B 11.97 14(3-Aminopyridin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l , 4] benzodioxanthene-8,3'-啕哚]-2'(1Ή)-ketoarlium bromide A 11.98 Ν-{2-[(2'-keto-2,3- Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-Γ(2Ή)-yl)methyl]pyridine-3- Base} A calcined amine B 11.99 Γ-(six rats ί* than -4--4-mercapto)-2,3-dihydro snail [Ρ夫鸣和[2,3-g] [1,4] Benzodioxantemene-8,3'-吲哚]-2·(1Ή)-ketohydrochloride C 11.100 Γ_{[1-(1-methylethyl)hexahydropyridin-4-yl] Methyl b 2,3-dihydrospiro[吱,[2,3-g][l,4]benzoic陆圜烯_8,3,_ρ丨哚丨哚]-2'(1Ή)-ketohydrochloride C 11.101 14(1-mercaptohexahydropyridin-4-yl)methyl]-2,3-di Hydron-bromo-[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-2'(1Ή)-one hydrochloride c 11.102 Γ-(吗福ρ林-2-ylindenyl)-2,3-dihydrospiro[2,3-g] [1,4]benzodioxanthene -8,3'-吲]-2'(1Ή)-ketone c 11.103 r-{ [4-(1-methylethyl)norfosin-2-yl]indolyl 2,3_dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene_8,3,_,5| 哚]-2\1Ή)-keto B 11.104 14(4-methylmorpholine-2-yl )methyl]-2,3-di-argon snail [Miso-[2,3-g][l,4]benzodioxanthene -8,3'-ρ 嗓]-2' (1Ή )-ketone B 143924-sp-20091127-6 -1019 - 201020257

Example No. Compound name IC5〇11.106 (8S)-l'-{[(2S)-4-methylmorphinyl-2-yl]methyl}-2,3-dihydrospiro [bite-and-[2, 3-Fantasy [1,4]benzodioxanthene-8,3,-吲"哚]-2'(1Ή)·ketone A 11.107 1'-{1>(trifluoromethyl wind bite_2 -yl] fluorenyl} snail [biting and [3,2-e][2,l,3]benzoxadiazole-8,3·-吲哚]-2Χ1Ή)-ketone C 11.108 6-chloro group -Γ-{[3-(Trifluoromethylcyclopyridin-2-yl)indolyl 2,3-dihydrospiro[吱,[3,2-f][l,4]benzodioxan Alkenes _9,3,_ 啕哚]-2'(ΓΗ)-ketone' C 11.109 1'-{[3-(trifluoromethyl)ρ 咬 -2--2-yl]methyl}-2,3 - Dihydrospiro[吱,[3,2-f][l,4]benzodioxanthene-9,吲哚]-2'(ΓΗ)-ketone C 11.110 1 _{[5-( - gas methyl) bite 0-n-yl]methyl}-2,3-diaza snail [pf-pyrano[2,3-g][l,4]benzodioxanthene] -2'(1Ή)-ketone A 11.111 5,6-Difluoro-indole-(hexahydropyridin-4-ylmethyl)spiro[1-benzo-p-pentan- 3,3'-吲嗓]hydrochloric acid Salt A 11.112 5,6-Difluoro-indole-[(1-methylhexahydro-p-buty-4-yl)indolyl]spiro[1_benzofuran-3,3'-啕哚]-2' (1Ή)-ketohydrochloride A 12 Ν-(cyclohexylmethyl)-3-[(2'-keto- 5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3'-β丨哚]-Γ(2Ή)-yl)methyl]benzoquinone Amine B 12.1 Ν-(2-methoxyethyl)-3-[(-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran -3,3'-4丨哚]-1'(2Ή)-yl)indolyl]benzamide B 12.2 Ν-hexyl-fluorene-methyl-3-[(2'-keto-5,6 - Dihydrospiro [benzo[i,2_b: 5,4-b]difurate-3,3W丨哚]-1'(2Ή)-yl)methyl]benzamide-5 12.3 Ν-(2 -ethylbutyl)-3-[(2'-keto-5,6-dihydrospiro[benzo[7:5,4-b]difuran-3,啕哚]-Γ(2Ή) -yl)methyl]benzamide B 143924-sp-20091127-6 -1020- 201020257

Example No. Compound name IC5〇12.4 N-(2,4-Dimercaptophenyl)_3·[(2'-keto_5,6-dihydrospiro[benzo[l,2-b: 5,4 -b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzamide B 12.5 3-[(2·-mercapto-5,6-dihydrospiro[ Benzo[1,2-b:5,4-b,]difuran-3,3·-吲哚Η'(2Ή)-yl)methyl]-N-(2-phenylpropyl)benzene Indoleamine B 12.6 N-[(1S)-1-cyclohexylethyl; keto- 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3, 3,-吲哚]-Γ(2Ή)-yl)hydrazino]benzamide B 12.7 N-[(1R)-1-cyclohexylethyl]_3_[(2,-keto-5-6- Dihydrospiro[benzo[l,2-b:5,4-b']difuran_3,3,_吲哚]-1,(2Ή)-yl)indolyl]benzamide C 12.8 Ν -(4-ethylphenyl)-2-[(2'-keto-5,6-dioxaspiro[benzo[l,2-b: 5,4-7]difuran-3,3,-吲哚]-1,(2Ή)-yl)methyl]benzamide D 12.9 Ν-(2-ethylphenyl)-2-[(2·-keto-5,6-dihydrospiro[ Benzo[l,2-b: 5,4-7]difuran-3,3'-啕哚]-1,(2Ή)-yl)methyl]benzamide C 12.10 Ν-(2,4 -Dimethylphenyl)-2-[(2'-fluorenyl-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] distiller -3,3'-啕哚]-Γ(2Ή)-yl)indenyl]benzamide C 12.11 Ν-(2-methoxyphenyl)-2-[(2'-keto-5,6 -Dihydrospiro[benzo[l,2-b:5,4-b]difuran,3,3'-indole]-indole (2Ή)-yl)methyl]benzamide C 12.12 Ν- (2-fluorophenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3'-哚哚]_1·(2Ή)-yl)methyl]benzamide-5 12.13 Ν-(3-phenylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo [U7: 5,4-b']difuran-3,3'-吲哚]-Γ(2Ή)-yl)methyl]benzamide C 12.14 Ν-(3-fluoro-2-yl) Phenyl)-2-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxan-3,3^5 ]-1'(2Ή)-yl)methyl]benzamide M 143924-sp-20091127-6 - 1021 -

201020257 If present, it is hydrogen, hydroxy, bromo, gas, cyano, fluoro, methyl, trifluoro*ethinyl, decyloxy; 曱 methoxy ethoxy, 2 methoxy ethoxy Oxyl, benzyloxy, 1-(tris-butoxycarbonyl)tetrahydropyrrole-3-yloxy, tetrahydropyrrole-3-yloxy, amine, sulfonylamino, sulfonylamine , [(Third-butoxy)-tetrahydropyrrol-3-yl]amino[6-decyloxypyridin-3-yl, 5-indolyl-1,2,4- 4 bis--3 a group, an amino (hydroxyimino)methyl group or a (tetrahydropyrrole-3-yl)amino group. In this particular embodiment, another embodiment is a compound of formula (IV) selected from the group consisting of: Γ-01 咬-2-ylmethyl) snail [吱 并[2,3-g] 喳噚Porphyrin-8,3,-吲哚]-2,(ΓΗ)-one; 1-(diphenylmethyl)spiroindole-3,3% dexeno[2,3-plex 1]benzofuran ]-2(1Η)-ketone; quinone diphenylmethyl) snail [(9) 哚-3,3,-sulfono[2,3-f][l]benzofuran]-2(1Η)-one 5 , 5'-dioxide; spiro-3,3'-carbo[2,3-f][l]benzofuran]_2(1Η)-ketone 5,5,-dioxide; Or 1-0 than bit -2-yl fluorenyl) 卜 哚 3,3,-喽 并[2,3-f][l]benzofuran]-2(1Η)-酉5, 5'-dioxide. L'-(4-decyloxybenzyl)-3-indolyl snail [bito-and-[2,3-f][i,2] benzisoxazole-7,3'-吲哚]-2 '(1Ή)-keto; 5-(non-oxy)-Γ-[(5-alkyl-2-nonyl)indenyl]spiro[μbenzofuran_3,κ哚]-2'(1Ή )-ketone; Γ-(diphenylfluorenyl)-6-methoxy-5-methylspiro[μbenzofuran_3 3,_w哚]_2, (1Ή)-ketone; 6-bromo-fluorene -(diphenylmethyl) snail [ι_benzoxanmol-3,3,_啕哚]_2, (1Ή)·ketone; Γ-(diphenylfluorenyl)-5,6-dimethyl snail [ι_笨和呋喃_3,3,_吲哚]_2, (1, 印-ketone; 143924-sp-20091127-l -104- 201020257

Example No. Compound Name IC5〇C 12.15 Team Heptyl-2-[(2|-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-1)'] Difuran-3 , 3'-啕哚]-1'(2Ή)-yl) fluorenyl;] benzoguanamine 12.16 Ν-(2-valley)-2-[(2'-keto-5,6-di Hydrogen snail [benzo[ι,2:7,5,4-b']difuran-3,3·-^1 哚]-l'(2,H)-yl)indenyl]benzoquinone B 12.17 Γ-[2-(hexahydro-p-bit-1-one-base) aryl]·5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxin- 3,3'-吲嗓]-2,(1Ή)-keto C 12.18 Ν-butyl-2-[(2'-keto-5,6-dihydrospiro[benzo[1,2:7:5 ,4-b'] bicinch-3,3'-嗍嗓]-1·(2Ή)-yl)methyl]benzamide C 12.19 Ν-(3-methylphenyl)-2-[ (2'-keto-5,6-dihydrospiro[benzo[i,2_b: 5,47']difuran-3J-吲哚]-Γ(2Ή)-yl)indenyl]phenylhydrazine Amine C 12.20 N-(2-|tyl-5-nonylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4] -b']二吱喃-3,3'-^卜朵]-ΐ,(2Ή)-yl) fluorenyl]benzamide C 12.21 Ν-(2,3-dimethylphenyl)-2 -[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3'-吲哚]-Γ(2Ή)- Base) Indoleamine C 12.22 Team ^^-曱Oxyphenyl ^ group ^-sing-keto group ^ each dihydrospiro-[i,2-b: 5,4-b']dipyran-3,3' -吲嗓]-ΐ,(2,Η)-yl)methyl]benzamide C 12.23 Ν-(3- gas fluorenyl keto-5,6-dihydrospiro[benzo[[7:5] ,4,7']difuran-3,3'-W哚]-Γ(2Ή)-yl)methyl ibenzamide C 12.24 N-[2-(4-phenylphenyl)ethyl]-2 -[(2i-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b]difuran-3,3'-吲哚Η'(2Ή)-yl)曱Benzoamine C 12.25 Ν·(2-曱-oxyphenyl)_4-[(2'-keto-5,6-dihydrospiro[benzo[nb:5,4-b']difuran -3,3'-吲哚Η'(2Ή)-yl)methyl]benzamide C 143924-sp-20091127-6 -1022- (8) 201020257

Example No. Compound name IC5〇12.26 4-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,47′]di-p-pyrene]-Γ(2Ή )-yl)methyl]good [2-(trifluoromethyl)phenyl]phenylguanamine C 12.27 4-[(2-keto-5,6-dihydrospiro[benzo[l,2- b : 5,4-b·]difuran-3,3·-吲哚]-1'(2Ή)-yl)indenyl]-N-phenylbenzamide B 12.28 Ν-mercapto-4- Κ21-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,吲哚]-Γ(2Ή)-yl)methyl]benzene Indoleamine B 12.29 Ν-(2-fluorophenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran- 3,3'-吲哚]-Γ(2Ή)-yl)methyl]benzamide-5 12.4- 4-((2'--yl-5,6-dihydrospiro[benzo[l,2- b : 5,4-b]di-n--3,3'-吲哚]-1'(2Ή)-yl)methyl]-N-(2-sulfenophen-2-ylethyl)phenylhydrazine Amine B 12.31 4-[(2^-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']diffin-3^-吲哚]-Γ(2Ή )-yl)hydrazino]benzamide A 12.32 Ν-(2,3-dihydro-1Η-茚-5-yl)-4-[(2,-keto-5,6-dihydrospiro[ Benzo[l,2-b:5,4,7,]difuran-3,3,-(6)哚]-1,(2Ή)-yl)methyl]benzamide C 12.3 3 Γ-[4-(morpholine-4-ylcarbonyl)benzyl]-5,6-dihydrospiro[benzo[l,2_b:5,4-b']difuran-3,吲哚] -2·(1Ή>ketone C 12.34 Ν-(2-ethylphenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4 VII']difuran-3,3'-啕哚]-Γ(2Ή)-yl)methyl]benzamide c 12.35 Ν-(2,6-monomethylphenyl)-4-[(2 '-Mercapto-5,6-dioxaspiro[benzo[l,2-b: 5,4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl Benzalamine c 12.36 Ν-(3-fluorophenyl)-4-[(2'-keto-5,6-di-argon][benzo[1,2-7:5,4-b'] Difuran-3,3'-throindole]-indole (2Ή)-yl)mercapto]benzamide B 12.37 Ν-(2,4-dimercaptophenyl)-4-[(2·-one) Benzyl-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']dipyran-3,3'-thirsty]-1'(2Ή)-yl)methyl] Benzoylamine B 143924-sp-20091127-6 -1023 · 201020257

Example No. Compound name IC5〇12.38 4-singer-keto- 5,6-dihydrospiro[stupid Hb: 5 4-7]difuran-3,3'-♦1](2Ή)-yl) Methyl]_N-seven-phene-2-ylmethyl) benzoguanamine B 12.39 N-ethyl-4-[(2·-keto-5,6-dihydrospiro[benzo[wb: 5, 4-b'] 吱 吱 哚 叩 叩 叩 评 评 评 12. 12. 12 12.40 N-(2-methoxyethyl)-4-[(2·-keto-5,6-dihydrospiro [Benzo[l,2-b: 5,4-b']di-p-flavor-3,3,-吲嗓]·ι'(2,η)-yl)indenyl]benzamide B 12.41 Team (2-ethoxyethyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] bicinch-3 ,3·-吲嗓]_ι'(2Ή)-yl)indolyl]benzamide B 12.42 Ν-cyclobutyl-4-[(2-keto-5,6-dihydrospiro[benzo[ 1,2 7:5,4-b'] Diterpenyl _3,3-^Budu]-1(2H)-yl)methyl]benzoguanamine B 12.43 4-[(--keto- 5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]di-p-pentan-3,3'-吲哚]-Γ(2Ή)-yl)indolyl]-Ν -1,3-, pizozol-2-ylbenzimidamide B 12.44 Ν-(3-fluoro-2-methylphenyl)-4-[(2'-keto-5,6-dihydrol Snail [benzo[l,2-b:5,4-b']di-p-pentan-3,3^bduo]-ΐ'(2Ή)-yl Methyl]benzamide C 12.45 Ν-(2-ethylbutyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[nb: 5,4-b] Furan-3,3'-(five)哚]-Γ(2Ή)-yl)indolyl]benzamide C 12.46 2-(2'-mercapto-5,6-diazaspiro[benzo[l,2 -b : 5,4-b']dipyridin-3,3.5bodo]-1\2'11)-yl)acetamide C 12.47 N-(4-ethylphenyl)-2- (2*-mercapto-5,6-diaza snail [benzo[1,2-7:5,4-bf]difuran-3,3'-啕哚]-Γ(2Ή)-yl) acetamidine Amine 'C 12.48 Ν, Ν-diethyl-2-(2·-keto-5,6-dihydrospiro [stupid [ub: 5,4 7'] difuran-3, 啕哚]-Γ (2Ή)-yl)acetamide B 12.49 Ν-(3,3-dimethylbutyl)-2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b : 5,4-b']difuran-3,3·-吲哚Η,(2Ή)-yl) acetamamine B 143924-sp-20091127-6 -1024 - 201020257

Example No. Compound name IC5〇12.50 N-[3·?:decylethoxy)propyl]-2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3,-啕哚]-indole (2Ή)-yl) acetamamine B 12.51 2-(2'-keto-5,6-dihydrospiro[benzo [i,2-b : 5,4,7,]difuran-3,3·-吲哚Η'(2Ή)-yl)-N-propylacetamide B 12.52 Ν-methyl-2-(2 '-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]dioxan-3,3,-,哚]-ΐ, (2Ή)-yl) -N-phenylacetamide B 12.53 Ν_(2,5-dinonylphenyl)-2-(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5 ,4-b']difuran-3,3,-吲哚]-1,(2'in-yl)acetamide C 12.54 N-(2,4-dimethylphenyl)_2_(2'_ Keto group _5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-throindole-1,(2Ή)-yl) acetamidine C 12.55 Ν-(2,3-Dimercaptophenyl)_2-(2|-keto_5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran -3,3,-吲哚]-1,(2Ή)-yl) acetamidine C 12.56 Ν-(2,6-diamidinophenyl)-2-(2'--yl_5,6_ Dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-indole (2Ή)-yl) acetamidine C 12.57 Ν-曱基-5-[(2·-oxaspiro[吱,[2,3<][1,3] benzodioxolanes-7,3'-^丨哚]-1' ( 2Ή)4)Methyl]-2-(trimethylmethyl)furan-3-carboxamide A 12.58 5-sodium-oxo snail [吱,[2,3-f][l,3]benzoic Oxytene-7,3,-bendo]-Γ(2Ή)-yl)indolyl]-2-(trifluoromethyl)indol-3-carboxyindole A 12.59 Ν,Ν-曱-5-5-[(2·-oxo[[,3,3-f][l,3]benzo) 1 oxy oxene-7,3'-吲哚]-1, (2, H)-yl)methyl]-2-(trifluoromethyl)anthran-3-carboxamide A 12.60 4-[(2'-keto-2,3-dihydrospiro[ollenyl][2 ,3-g][l,4]benzodioxanthene-8,3·-峋哚]-Γ(2'Η)-yl)methyl]benzamide A ____——- 12.61 3 -[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-thirsty]-1 ·(2Ή> base) fluorenyl] benzoguanamine B ———* 143924-sp-20091127-6 -1025 - 201020257

Example No. Compound name ic5〇12.62 N,N-Dimethyl-3-[(2'-keto-2,3-dihydrospich-[2,3_g][1,4]benzodiox圜 圜 -8,3'-t»5 丨哚] a) methyl] benzoguanamine a B 12.63 N-mercapto-2-[(2'-keto-2,3-dihydrospiro[吱 并 [2 3_g][1,4] benzodioxanthene 浠-8,3'-β 卜 ]]_ι·(2,η)-yl) fluorenyl] pyridine-3-carboxyguanamine C 12.64 Ν-(2-Aminoethyl)-2-[(2'-keto-2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxan)圜 _8,3'_ρ5丨嗓]—ι,(2,η)_yl) fluorenyl]p than 唆-3-treazone dihydrochloride B 12.65 N-(2-fluorophenyl)- 4-[(2'-keto-2,3-dihydrospiro-u Nan [2,3-g][l,4]benzodioxanthene_8,3,_沔丨嗓] _ι,(2Ή)_ base) thiol]benzamide B 13 5-[(2 -mercapto-5,6·>-a nitrogen snail [stupid [l,2-b: 5,4 seven] ]二咬0南-3,3'-吲哚]-Γ(2Ή)-yl)methyl]pyran-2-carboxylic acid C 13.1 Ν,Ν-dimethyl-5-[(2·-keto) -5,6-dihydrospiro[benzo[i,2-b : 5,4-b']difuran-3,3'-啕哚]-l'(2,H)-yl)methyl]吱 -2--2-carboxyguanamine A 13.2 Ν-methyl-5-[(2'-keto-5,6-dihydrospiro[ And it seems like seven: 5,4-b,] two biting -3,3'-thirty 哚]-1, (2, Η)-yl) methyl] gnashing _2 carboxy carbamide B 13.3 2-[ (2'-keto-5,6-dihydrospiro[benzo[1,2-b: 5,4-7,]difuran-3,3 p-]-1'(2Ή)-yl) fluorenyl ]-i,3-p#嗤_4_延醯amine B 13.4 N,N-dimercapto-2-[(2·-keto-5,6-dihydrospiro[benzo[i,2- b : 5,4-b']dipyran-3,3'-called 哚]-Γ(2Ή)-yl) fluorenyl]-1,3^ azole-4-carboxyguanamine B 13.5 Ν-ring Propyl-2-[(2'-oxaspiro[2,3-f][l,3]benzodioxol-7,3,-W哚]-l, (2, H)-yl)methyl]-1,3-oxazole-4-carboxamide A 13.6 N-(l-曱^ethyl)-2-[(2,-oxo[[ 3-f][l,3]benzodioxanthene-7,3'-吲哚]-1,(2Ή)-yl)indolyl]-1,3-oxazole-4-carboxyguanamine A 143924-sp^20091127-6 -1026 - 201020257 实例 Example No. Compound name 13.7 N-(2-lphenyl)-2-(2: keto-2,3-dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene _8,3,_吲嗓]yl)acetamide 13.11 Ν-[3-(2·-keto-5,6-dihydrospiro) [Benzo[ι,2:7,5,4-b,]dioxan-3,3·-ten]-1·(2Ή)-yl)propyl]_2-(trifluoromethoxy Benzomethine 14 l'-[(2S)-2-propyl]-5,6-dihydrospiro[benzo[1,2-7:5 4-b,]difuran-3,3·-嗍哚]-2'(1Ή)-ketone'- 14.1 l'-[(2S)-2-(yloxy)propyl]-5,6-dihydrospiro[benzo[1,2:7:5 ,4-b]difuran-3,3,?| 哚]-2'(1Ή)-one 14.2 l'-{(2S)-2-[(4-1benzyl)oxy]propyl b 5 ,6_Dihydrospiro[benzo[l,2-b:5,4-b']diazin-3,3'-叼1]-2'(1Ή)-one 14.3 14.4 14.5 15.1 15.2 15.3 15.4 l'-[(2S)-2-indenyl-2-ylmethoxy)propyl]_5,6-dihydrospiro[{,2-b: 5,4-b']吱 _3,3'-巧丨嗓]-2'(1Ή>· Stuffed | Γ-(3-hydroxybutyl)-5,6-dihydrospiro[benzo[i,2-b: 5, 4 VII,] 唉 -3 -3,3·-吲哚]-2Χ1Ή)-ketone,-(4,4,4-tris-3-hydroxybutyl)-5,6-dihydrospiro [U_b : 5,4-13]difuran-3,3'-啕哚]-2'(1Ή)-ketooxime-{3-[(3-methylbutyl)amino]propyl}-5 ,6-Dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3,-叼丨哚]-2'(1Ή)-ketohydrochloride Γ-{3 -[butyl(indenyl)amino]propyl}-5,6-dihydrospiro[{,2-b:5,4-b']difuran-3,3'-吲哚] -2·(1Ή)- ketone hydrochloride 1·-{3-[(2,2,2-three defeated B Amino]propyl}-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-W 哚]-2,(1Ή)· Ketone hydrochloride 3-{[3-(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]di-amino-3,3'- W嗓]-Γ(2Ή)-yl)propyl]amino}propionitrile hydrochloride-(diguanyl)pyridin-3-yl H4(2R)-tetrahydrofurazone-2-ylmethyl] -5,6-dihydrospiro[benzo[l,2-b:5,4?|] dioxin--3,3'-叼|fluorenone 143924-SP-20091127-6 -1027 - 4' - 16 201020257

Example No. Compound name ic5〇16.1 4'-[(E)-2-(4-fluorophenyl)vinyl]44(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzene And [i,2-b : 5,4-b]difuran-3,3·-吲哚]-2'(ΓΗ)-keto B 16.2 Αdibenzo[b,d]sulfon-4-yl -1,-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-吲哚]-ΑΓΗ)-ketone B 16.3 4'-(1-benzoporphinyl)-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzene And [1,2-b : 5,4-b']difuran-3,3,-chico]-2'(ΓΗ)-ketone C 16.4 4'-(1-methyl-1Η-叼丨哚-5-yl)-l,-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran -3,3,-吲哚]-2'(1Ή)-keto B 16.5 4'-[3,5-bis(trifluoromethyl)phenyltetrahydrofuran-2-ylmethyl]-5,6-di Hydrogen snail [benzo[i,2-b : 5,4-b,]difuran B 16.6 4'-(4-phenoxyphenyl)-l'-[(2R)-tetrahydrofuran-2-yl Base]_ 5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-吲哚]-ΑΓΗ)-one B 16.7 4'-[4 -(2-methylpropoxy)phenyl]_14(2R)_tetrahydrofuran-2-ylmethyl] -5,6-dihydrospiro[benzo[i,2-b:5,4-b.]difuran-3,3'-啕哚]-2'(1Ή)-one B 16.8 4-(4 -butoxyphenyl)_1'-[(2)-tetrahydroglyptyl-2-ylmethyl]_ 5,6-dihydrospiro[benzo[i,2-b : 5,4-b ']二吱喃-3,3Ί 哚]-2'(ΓΗ)-ketone B 16.9 4-(4-methoxyphenyl)44(211)-tetrahydrofuran-2-ylmethyl]_5 6-dihydrospiro [Benzo[1,2-b : 5,4-b']difuran-3,3,-吲' 哚]-2·(1Ή)-ketone A 16.10 4'-gypdin-5-yl-1 ,-[(2R)-tetrahydrofuran-2-ylindolyl snail [benzo[l,2-b:5,4-b,]difuran-3,3,-吲哚]-2'(1Ή)- Ketone C 16.11 4_[6-(didecylamine aridin-3-yl)-1'-{[5-(trifluoromethyl) odor-2-yl]methyl}-5,6-dihydro Snail [benzo[l,2-b: 5,4,7,]difen-3,3'-吲哚]·2·(1Ή)-ketone----- B 143924-sp-20091127- 6 -1028 - 201020257

Example No. Compound name IC5〇16.12 卜[(5-Gas-2-ylenoyl)methyl]_4,-[6-(didecylamino)>pyridin-3-yl]spiro[吱和[ 2,3-f][l,3]benzodioxanthene _7,3'-< 哚]-2'(1Ή)-class B 16.13 卜[(^气基-2- far phenyl )methyl]·4, 〇 喃 ) ) 螺 [吱, 吱 弁 [2, 3-f] [l, 3] benzodioxene _ _7, 3' _ 丨哚 酮 ketone B 16.14 4 '-[6-N-methylamine oxazolidine _3_yl] snail [biting sputum and yang sputum (3) benzodioxan scorpion -7,3·-啕咮]·2,(1Ή)-ketone C 16.59 4 -(6-(dimethylamino)> than biting_3_yl)_1'_(? than bite_2_ylmethyl)_3,7_dihydro-2Η-spiro[benzofuran[5,6_b ][14]Dioxoyuan 'ene-8,3'-dihydroanthracene]-2'-keto B 16.60 4'-(4-methoxyl)-1'-(acridin-2-yl)曱3)_3,7_Dihydro_2H_ snail [benzofuro[5,6-b][l,4]dioxanthene-8,1-dihydroanthracene-2'-one A 16.61 (7S)-4·-味喃基-Γ-Methyl snail [吱,[2,3-f][l,3]benzo-oxo-oxan -7,3^巧丨嗓]嗣A 16.62 (7R)-4·-furan-3-yl-indole-methyl spiro[p-f-[2,3_f][i,3]benzodioxanthene-7,3'-吲嗓]-2,(1Ή)-嗣B 16.88 1 -[(5-gas base - 2-ρ塞 基 yl) fluorenyl]-5-(6-methoxy ρ 鸣 -3-yl) snail [1-benzofuran-3,3·-峋哚]-2, (1Ή)- Ketone C 17 Γ-(4-hydroxybenzyl)-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]difuran-3,3'-吲哚]-2Χ1Ή )-Sun A 17.1 Γ-(4-benzyl)·2,3-dihydrospiro[吱,[2,3-g][l,4]benzodiazepine-8,3· -峋哚]-2·(1Ή)-net A 17.2 Γ-(3-, propyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzoic Oxygen decene-8,3'-吲哚]-2·(1Ή)-class A 18 2'-keto-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene-8,3'-吲哚]-1, (2Ή)-carboxylic acid ethyl ester A 18.1 4'-bromo-2'-oxo snail [吱 并[2,3 -f][l,3]benzodioxol-7,吲哚]-ΐ·(2Ή)-carboxylic acid tert-butyl ester A 18.2 2'-keto-2,3-dihydrospiro [吱吱[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-1,(2Ή)-carboxylic acid tert-butyl ester B 143924-sp -20091127-6 • 1029 · 201020257 Example number Compound name icso 19 1'-{[(3 into 5 feet, 533, 8 & 5 feet) -2,2,7,7-tetradecyltetrahydro-3 -双[1,3]·—Oxygen oxime and [4,5-b : tS'-d]'1 basement-5-yl]methyl}-2,3- Hydrogen snail [Miso-[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one C 20 6-~^ -6 -(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3·-吲哚]-1' (2Ή)-yl)-D-half-milk sucrose C 21 Γ-cyclopropyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Terpene-8,3'-吲哚]-2'(1Ή)-_ A 22 Γ-acetamido-2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene-8,3'-oxime,dol]-2'(1Ή)-鲷A 23 [-{[4-(trifluoromethyl)acridin-2-yl]methyl}- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3,_ 哚 哚]-2'(1Ή)-ketone A 28 Γ -[3-(3-methyl-1,2,4-«»di-salt-5-yl)indolyl]-2,3-dihydrospiro[pf-pyrano[2,3-g][ 1,4]benzodioxanthene-8,3,-吲哚]-2'(1Ή)-ketone A 29.1 Γ-[4-(3-Amino-1Η-pyrazole-5-yl) Benzyl]-3-methyl snail [, succinyl[3,2-f][l,2] benzoiso-p-β sitting_5,3'-υ5 budu]-2'(1Ή)-ketone Hydrochloride B 29.2 Γ-[4-(3-Amino-1Η-pyrazol-5-yl)benzyl]-2,3-dihydrospiro[吱,[2,3-g][l,4 Benzodioxanthene _8,3,5丨哚]-2'(1Ή)- Hydrochloride----- B 30 1'-[4-(3-indolyl-1,2,4-oxadiazol-5-yl)-yl]-2,3-dihydrospiro[吱And [2,3-g][l,4]benzodioxanthene-8,3'-吲' 哚]-2'(ΓΗ)-ketone- A 31 2·-keto-oxime-01 Bis-2-ylindenyl)-1·,2,2·,3-tetrahydrospiro[2,3-g][l,4] benzodioxanene-8,3W丨哚] -5·-Carboxyguanamine ------ B 32 Γ-[(6-morpholino-4-ylpyridin-3-yl)indolyl]-2,3-dihydropyrano[2,3 -g][l,4]benzodioxanthene-8,吲哚]-2'(1Ή)-one------- A J---

143924-sp-20091127-6 •1030- 201020257 实例 Example No. Compound name 32.1 32.2 1'-{[6-(dimethylamino)>pyridinyl]methyl}-2,3_dihydrospiro [bite喃[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2Χ1Ή)-ketooxime-{[6-(didecylamino) later pyridine- 2-yl]methyl}-2,3-dipyrano[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(ΓΗ)- Ketone 33.2 5,6-difluoro-l'-{4-[(3R)-tetrahydro-p-l-yl-3-ylamino]] cycline}-[1-benzofuran-3,3'-吲哚]-2{1Ή)-ketohydrochloride ' 33.3 -[(5-morpholine piperidin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g ][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one 33.4 35 35.1 36 37 38 39 -{[5-(dimethylamino) Pyridin-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]- 2'(1Ή)-ketooxime-[(6-keto-1,6-dihydropyridin-3-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g] [l,4]benzodioxanthene_8,3%5丨哚]-2'(1Ή)-keto 14(2-hydroxypyrimidin-5-yl)methyl]-2,3-dihydro Snail [吱, P, P, 3-g] [l, 4] benzodioxanthene-8,3,-叼丨哚]-2,(1Ή)-keto'-[(1-mercapto-6-keto-1,6-dihydroρ-buty-3-yl)indenyl]-2,3-dihydrospiro[吱 并[2,3-g][l,4]benzodioxanthene -2]-2'(1Ή)-ketone 1'-[(6-amino ρ than -3-yl) Methyl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanene-8,3'-嘀哚]-2'(1Ή)- Ketooxime '-trans-yl-indole-{5-[(2'-keto-2,3-dihydrospiro[pfumandan[2,3-g][1,4]benzodioxanthene) Alkene-8,3'-吲嗓]_1'(211)-yl)indenyl]pyridin-2-yl}-bromoimidoguanamine-([1,2,4]triazolo[l, 5-a]pyridin-6-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3,_吲哚]-2 乂1Ή)-ketone 143924-sp-20091127-6 -1031 - 201020257 6-(low oxy)-barium benzoyl) snail [1-benzofuran_3 3ι·ρ? _2, (1 Ή ketone; Γ-(diphenylmethyl)_5-fluoro-6-methoxyspirobenzofuran _3,3,嘀哚]_2, (1Ή) ketone; Γ-(two Benzyl)-5-1 snail [1-benzofuran_3,3,_ 哚 哚]_2,(1Ή)__ ; 1 -(a succinylmethyl)-6-methoxy snail [1_ Benzofuran_3,3,吲哚]_2ι(1Ή)_嗣; 6-(loweroxy)-1 -(3-methylbutyl) snail [μ笨和furan_ 3 3,吲哚]_2,(1Ή)-ketone; 6-bromo-l'-{[5-(trifluoromethyl)pyran-2-yl]indenyl}spiro[丨benzofuran_3 , 3W丨哚]-2·(1Ή)-ketone; _ 5-bromo-1'-{[5-(trifluoromethyl) succinyl-2-yl]methyl}spirobenzofuran-3 3 ,吲哚]-2·(1Ή)-ketone; 6-decyloxy-5-methylspiro[1_benzofuran_3,3,啕哚]_2,(1Ή)嗣; 6-bromo snail [1-Benzofluorene_3,3Ί嗓]_2, (1 ugly)-ketone; 5,6-dimercaptospiro[1-benzofuran_3,3,_ρ?丨哚]_2, (1Ή Ketone; 5-fluoro-6-methoxyspiro[ι_benzofuran_3,3,吲哚]_2,(1Ή)-one; 5-fluoro-spiro[1-benzopyrene_3 , 3Ί 嗓]_2, (1Ή)__ ; 6_曱oxyspiro[μbenzofuran_3,3,-吲哚]ΚΓΗ)-one; 6-hydroxyspiro[1-benzopyrene_3, 3, _ρ?丨哚]_2, (ΓΗ)·steel; 1 (a succinylmethyl)-6-pyloryl[μbenzofuran_3,3,-(penta)-(10)) ketone; 3- {[Γ-(diphenylmethyl)_2,-keto-_r, 2L dihydrospiroindole benzofuran] each]oxy}tetrahydropyrrole + carboxylic acid third-butyl ester; 3 [( 2 keto 1,2-monohydrospiro[μbenzofuran-3,3,_啕哚]yl)oxy]tetrahydropyrene 0 each-1-lowering acid 苐三-丁格(; 3S) 6 Methoxy-5-methyl snail Benzene biting 嗔3,3·弓布朵]_2 mouth condition)-ketone; (3R) 6曱oxy-5-methylspiro[lbenzofuran_3,3,_μ丨哚](10)) Ketone; 143924-sp-20091127-1 •105· 201020257 Example No. Compound name ic5〇40 l'-[(2S)-2,3-dipropylpropyl]-2,3-dihydrospiro[吱[2,3-g] [1,4]benzodioxanthene-8,3'-啕哚]-2·(1Ή)-class B 41 6-[(2'-keto-2, 3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-1·(2Ή)-yl)methyl]p Bipyridyl-2-carbonitrile A 42 6-[(2'-keto-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene- 8,3'-吲哚]-Γ(2Ή)-yl) fluorenyl]p-pyridin-2-carboxyguanamine A 44 3-amino-indole-(4-methoxybenzyl) snail And [3,2-f][l,2]benzisoxazole-5,3'-啕哚]-2'(1Ή)-keto B 44.1 3-Amino-indole-(acridin-2- Methyl) Cyclobuphtho[3,2-f][l,2] benzisoxazole-5,3'-Η丨哚]-2'(1Ή)-keto B 44.2 3-Amino -1'-[(2 ft)-tetrahydrofuran-2-ylmethyl] sulphide [吱,[3,2-:〇[1,2] benzohedo] gt, saliva-5,3'-吲嗓]-2'(1'11)-keto C 44.3 3-amino-1·-[2-(trifluoromethyl) yl] snail [吱And [3,2_f][i,2] benzoisoxazole-5,3'-啕哚]-2'(1Ή)-keto C 45 6-trans-yl-2'-keto-l'-[ (2R)-izg hydrogen thiophene-2-yl hydrazide]_ι,,2,_ Dihydrospiro[1-benzofuran-3,3'-吲哚]-5-carbonitrile' C 45.1 6-hydroxyl -2'-keto-1'-[2-(trifluoromethyl) aryl; μ!,, 〗, · Dihydrospiro[1-benzofuran-3,3'-吲哚]-5- Formonitrile C 46 1'-[2-(Trifluoromethyl)-yl]-1Η- snail [ρ夫南和[3,2_η吲〇坐-5J-吲哚]-2'(1Ή)-ketone C 46.1 1'-indole bite-2-ylmethyl)-1Η-spiro[吱,[3,2-f]carbazole-5,3,-吲哚]-2'(1Ή)-keto B 46.2 Γ-((3-(trimethylmethyl)>pyridin-2-yl)methyl)_1,6-dihydrospiro[Octa[3,2-fH丨 -5-5,3'-dihydro丨嗓]_2'-giq B Biological Example 2 Electrophysiological Test (In Vitro Assay) The cells expressing the channel of interest in our body are 〇.5 mg/ml G418, +/-1% PSG and 10% heat. Inactivated bovine fetal serum was cultured in DMEM growth medium 143924-sp-20091127-6 -1032-201020257 (Gibco) at 37 ° C with 5% CO 2 . For electrophysiological recording, cells were plated on 10 mm culture dishes. Whole-cell recordings were performed using the established whole-cell voltage clamping method (Bean et al., in cold//遽/方尹) using the Axopatch 200B amplifier and Clampex software (Axon Instruments, Union City, CA). All experiments were performed at ambient temperature. The electrode is fired to a 2-4 Mohm resistor, and the voltage error and capacitance artifacts are minimized by series resistance compensation and capacitance compensation. The data was taken at 40 kHz and filtered at 5 kHz ® . The external (bath) solution contained: NaCl (140 mM), KC1 (5 mM), CaCl2 (2 mM), MgCl2 (1 mM), and HEPES (10 mM) at pH 7.4. The internal (pipette) solution contains (expressed in mM): NaCl (5), CaCl2 (0.1), MgCl2 (2), CsCl (10), CsF (120), HEPES (10), EGTA (10) at pH 7.2 . To estimate the steady state affinity of the compound for the stationary and inactive states of the channel (individually Kr and Ki), a depolarizing voltage of -60 to +90 mV from a holding potential of -120 mV is used, using a 12.5 millisecond test pulse to Establish a current-voltage ^ relationship (IV curve). The voltage close to the IV-curve peak (-30 to 〇 mV) was used as the test pulse throughout the remainder of the experiment. A steady state deactivation (validity) curve is then constructed by measuring the current activated during the 8.75 millisecond test pulse after adjusting the pulse for a period of 1 second to _10 mV. The steady state voltage-dependent binding of the compound to the sodium channel is measured by blocking the ion current at two holding potentials. Bonding to the quiescent state channel is measured by using a holding potential of -120 mV to achieve maximum utilization. The channel bound to the inactive state was evaluated at the holding potential, and only 10% of the channels were available for opening at 143924-sp-20091127-6 -1033 · 201020257. The membrane potential is maintained at this voltage for at least 10 seconds so that drug binding can be balanced. The apparent dissociation constant at each voltage is calculated using the following equation: % inhibition = [drug] 7 Γ drug] + 3⁄4) where Kd is the dissociation constant 4 or ^), and [drug] is the concentration of the test compound. When tested in this mode, representative compounds of the present invention exhibit affinity for the inactivation state of the channel of interest of interest as set forth in Table 3 below, where "A" means & less than 300 nM, And "B" means & is larger than the outline. The number of examples provided in Table 3 corresponds to the examples in this paper: Table 3 Example No. Compound Name Ki (靡) 1.2 1 - (峨唆f-based methyl group > 2 , 3_ dihydrospiro [biting [1,4] benzodioxan 浠8,3,_吲哚]_2,(1Ή)__ --------- B 1.10 (3S)- 5'6-_hydrogen snail [benzoan from: 5,4,7,]difuran_3 3, 吲哚]-2^:1Ή>·_ , A 1.11 (S)-2,3-dihydrospiro [吱喃和[2,3-g][l,4]benzone-8,3'-v»5卜朵]-2,(ΓΗ)-ketone----- B 1.12 (8S)- R-{[3-(Trifluoromethylcyclopyridin-2-yl)methyl b 2, Factory: I-hydrospib- oxa[2,3-g][l,4]benzodioxan '圜^ -8,3,-Qiao noise】_2.(1Ή> Ketone round---- A 1.13 (8S)-1'-K5-pyridylpyridine, 2-yl)methyl]_2,3 II ^ carboxy[2,3-g][l,4]benzodioxolene _8 3,_吲哚]-2'(ΓΗ)-ketone ------ A ----- ~~--- 143924-sp-20091127-6 -1034 201020257

Example No. Compound name K|(/dVI) 2.27 6-((5-(Trifluoromethyl)pyran-2-yl)methyl)-2,3,3',7'-tetrahydro-2Ή-snail [[1,4]dioxolynene[2,3-f]indole-8,8,-benzofuro[5,6-b][l,4]dioxolene]- 7(6H)-keto A 2.34 2,2-difluoro-indole-{[5-(trifluoromethyl)anthracene]-N-2-yl]methyl}spiro[furo[2,3-f][ l,3]benzodioxanthene-7,3·-吲哚]-2·(ΓΗ)-keto B 2.35 2,2-difluoro-indole-{ [5-(trifluoromethyl)anthracene喃-2-yl]methyl}spiro[furo[2,3-f][l,3]benzodioxol-7,3·-吲哚]-2·(1Ή)-keto B 2.54 Γ-{[3-(Trifluoromethyl oxaridin-2-yl) fluorenyl}-7,8-dihydrospiro[1,4-dioxopinene [2,3-g][l , 3] benzodioxanthene-4,3W丨哚]-2Χ1Ή)-keto B 2.65 6-[2-(2-methoxyethoxy)ethyl]_2,2\3,3' -tetrahydrospiro[1,4-dioxoisene[2,3-fH哚-8,8·-trimethane[2,3-g][l,4]benzodioxanthene ]_7(6Η)-嗣B 3 6-Methoxy-5-mercaptospiro[1-benzofuran-3,3,-啕哚]-2,(1Ή)-one B 3.29 6-methoxy -2'-keto-1,2'-dihydrospiro[1-benzofuran-3,3·-clear]-5-indolecarbonitrile B 3.33 4'-fluoro group- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,?丨哚]-2'(1Ή)-_ A 3.34 4 '-Porphyrin-3-yl-2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxanthene-8,3'-thirsty]-2 '(1Ή)-net B 3.35 4'-(4-phenoxyphenyl)-2,3-dihydrospiro[吱,[2,3-g] [1,4]benzodioxan Alkene _8,3W 丨哚]-2'(1Ή)- 颜 IB 3.41 snail [[,2,2-e][2,l,3]benzoxadiazole-8,3,- 哚]- 2|(1Ή)-keto B 4 1'-(tetrahydro-2Η- sher-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b : 5,4 -b1]difuran-3,3,-吲哚]-2,(ΓΗ)-keto B 4.3 r-[(2R)-iahydrofuran-2-ylmethyl]-5,6-dihydrospiro[ Benzo[l,2-b:5,4-b']difuran-3,3·-thrylene]-2,(1Ή)-keto B 143924-sp-20091127-6 - 1035 - 201020257

Example No. ---- Compound Name _) 4.6 1 -(Tetrahydro-2H-pyran-4-ylmethyl)-5,6-dihydrospiro[Benzo[l,2-b: 5,4七'] 二吱味-3,3'-令展1_2丫], state, B 4.8 1 monooxo-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2- b : 5,4-b']difuran-3,3Ί 嗓]_2·(ι,η)_嗣一' B 4.10 1 -(tetramium-2Η-Ι» bottom σ -3--3-methyl) -5,6-dihydrospiro[benzo[l,2-b:5,4?']-p-pentan-3,3'-recovery]_2'(i,hvketone B 4.16 1 -(four Hydroquinone-3-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b.]dipyran-3,3'-吲哚1_2, (峒-峒B 4.20 r-(propylene oxide-2-ylmethyl^-[l,2-b : 5,4-b']di-p-amyl-3,3,-啕哚ua'HV ketone B 4.22 3-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5 4-b,]-carbo-3,3'-thirsty]-1' (2Ή )-yl)methyl]benzene+nitrile B 4.22 3-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5 4-b1] -pyran-3,3 %?丨哚H,(2,H)-yl)indenyl]benzene+nitrile B 4.27 1·-(2,1,3-benzoxadiazole_5_ylmethyl)_5 6 dihydrospiro [ Benzo[l,2-b. 5,4-b'] two bite _3,3'_叫丨嗓]_ 2,(1Ή)- Ketone B 4.28 Γ-(2,1,3-benzothiazol-5-ylmethyl)_5,6-dihydrospiro[benzo[l,2-b. 5,4-b'] two bites Ρρ朵]- 2ΧΓΗ)-ketone A 4.29 Γ-[(4 bucket carbaryl-2-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4 VII'] dioxin-3,3'-啕嗓]-2'(1Ή)-keto B 4.36 1·-(3-methylbutyl)-2,3-dihydrospiro[吱喃和[2 ,3_8][1,4] benzodioxanthene A 438 Γ-(tetrahydro-2-indole-piperidin-2-ylmethyl)-2,3-dihydrospiro[furo[2,3- g][l,4]benzodioxanthene_8 3'_ρ丨哚丨哚]-2'(1Ή)-ketone A 4.43 1,-[(23)-tetrahydrofuran-2-ylindenyl]- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene·8,3′_吲哚;μ 2′(1Ή)-keto B

❹ 143924-sp-20091127-6 - 1036 -

(S 201020257

Example No. Compound name KiifM) 4.45 Γ-(1,4-dioxoindole_2_ylindenyl)-2,3_dihydrospiro[Crunched [2,3-g][l,4]benzene Dioxetine-8,3,-吲哚2'(ΓΗ)-嗣B 4.48 1-(2,3-一风-1,4-benzodioxanthene-6-ylmethyl )_ 2,3-Dihydrospiro [snake P,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2,(1Ή)-ketone A 4.49 (RH'-{[5-(Trifluoromethyl)pyran-2-yl]methyl}_2,3_dihydrospiro[吱,[2,3-g][l,4]benzoic Oxygen lanthanum -8,3'-吲哚]-2'(1Ή)-ketone A 4.50 (3)-1'-{[5-(trifluoromethyl)anthracene]methyl}-2 ,3_Dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8,吲哚]-2|(1Ή)-ketone A 4.51 (S)-l '-(Pyridin-2-ylmethyl)-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxene _8,3'_吲哚] _ 2·(ΓΗ)-ketone A 4.54 1'-{[5-(Trifluoromethyl)pyran-2-yl]methyl}-3,4-dihydro-2Η-spiro[吱喃[2 ,3-h][l,5]benzodiazepine heptarene-9,3·-啕哚]-2·(1Ή)-辋A 4.55 Γ-0-pyridin-2-ylmethyl)- 3,4-Dihydro-2Η-spiro[,[2,3-h][l,5]benzodioxyl octadecene_9,3'-吲哚]-2'(1Ή)- B 4.68 6-Methoxy-r-[(2R)-E9hydrofuran-2-ylmethyl]spiro[1_ benzofuran-3,3'-啕哚]-2(1Ή)-one B 4.103 4'-(4-phenoxyphenyl)_Γ_(pyridine_2_ylindenyl)_2,3_dihydrospiro[,,[2,3-g][l,4]benzodioxan Terpene A 5.1 7'-Chloro: 1'-((5-(Trifluoromethyl)-antho-2-yl)indenyl)_5,6-dihydro-2-indole-spiro[benzocypano-pyrano[ 6,5-b]furan-3,3,-dihydro 4丨哚]-2'-one A 5.4 (3R)-r-indolepyridyl-2-ylmethyl)-5,6-dihydrospiro [Benzo[l,2-b:5,4-b]difuran-3,3,-啕哚]-2, (1Ή>gt; ketone B 143924-sp-20091127-6 •1037- 201020257

Example No. Compound name Ki(fM) 5.5 (3R)-l'-{[5-(Trifluoromethyl) taste. South_2_yl]methylbu 5 6_dihydrospiro[benzo[l,2-b : 5,4-b']difuran-3,3,-W 哚]-2'(ΓΗ> ketone B 5.6 (3S)-r-(pyridin-2-ylindenyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-啕哚]-2,(1Ή)-keto B 5.7 (3S)-r-{[5-(_E_ fluoroindolyl) succinyl-2-yl]methyl}-5,6-dihydrospiro[benzo [l,2-b : 5,4-b']dipyran-3,3'-^丨哚]-2'(1Ή)-ketone A 5.17 (8S)-r-[(2-methoxyl) Pyrimidin-5-yl)indenyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene_8,3,_啕哚]- 2'(1Ή)-ketone A 5.18 (8S)-l'-(°^bit-2-ylmethyl)-2,3-dihydrospiro[ρ失喃[2,3-g][l, 4] benzodioxanthene-8,3,?丨哚]-2'(1Ή)-ketone A 7.4 Speaking)-1'-pentyl-2,3-dihydrospiro[味喃[2 ,3$][1,4]benzodioxanthene-8,3W|哚]-2·(1Ή)-keto B 7.8 Γ-(4-decyloxybutyl)-2,3-di Hydrogen snail [吱味和[2,3-g][l,3]benzodioxanthene-8,吲哚]-2'(1Ή)-ketone A 7.15 (8R)-l'-{[ 3-(Trifluoromethyl)>pyridin-2-yl]indenyl}_2,3-dihydrospiro[吱,[2,3-g][l,3]benzodioxanthene -8,3'-啕哚]-2'(1Ή)-keto B 8.4 Γ-pentyl-2,3- Hydrogen snail [吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-ketone A 8.6 (8R)-r- [(2S)-l,4-dioxolyl-2-ylmethyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Alkenyl-8,3'-indole]-2'(1Ή)-keto B 8.7 (8S)-1'-[(2S)-1,4-dioxoindolin-2-ylmethyl]-2, 3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-啕哚]-2'(1Ή)-keto B • 1038 - 143924 -sp-20091127-6

(S 201020257

Example No. Compound name Ki(/zM) 8.8 which)-14(211)-1,4-dioxoindolin-2-ylmethyl]-2,3-dihydrospiro[吱,[2,3- g][l,4]benzodioxanthene-8,3'-叼布朵]-2'(1Ή)-ketone A 8.12 l'-[(2R)-l,4-dioxane -2-ylmethyl]-3,4-dihydro-2-indole-spiro [bito-and-[2,3-h][l,5]benzodiazepine decylene]-2' (ΓΗ )-keto B 9 3-methyl-indole-{[5-(trifluoromethyl)pyran-2-yl]indenyl}spiro[furo[3,2-f][l,2]benzo Isoxazole _5,3'_啕哚]-2'(ΓΗ)-ketone A 9.6 1 -(°3⁄4 ate-4-ylmethyl)-5,6-dihydrospiro[benzo[1,2 7: 5,4-b']difuran-3,3'-indole]-2'(1Ή)-keto B 9.20 decyloxyethoxy)ethyl]_2,3_dihydrospiro And [2,3-g][l,4] benzodioxanthene _8,3,_吲哚]_ 2,(1Ή)-ketone A 9.23 4-methyl-r-[(2R) -rahydrofuran mercapto] Η 螺 螺 [[,,,,,,,,,,,,,,,, 4Η)-dione B 9.24 3_methyl-Γ-01 than bit -2-yl fluorenyl) snail [吱,[3,2_q [1,2] benzopyrene, scent-5,3'-吲嗓]_2,(i'h)-keto B 10.1 Γ-(acridin-3-ylmethyl)-2,3-dihydrospiro[吱 并[2 3_g] [1,4] And oxy-terpinene-8,3·-, 嗓]] 2'(ΓΗ)-ketone B 11.14 1 _[4-(5-methyl-1,2,4-oxadiazol-3-yl)午基]_5,6_Dihydrospiro[benzo[l,2-b:5,4-1)']2,3'-side 1-2-((1Ή)-ketone A 11.27 Η3-(5-曱^ -1,2,4』二嗤-3·基)Pyl]_5,6 dihydrospiro[benzo[l,2-b : 5,4-b·] Gorge π南·3 3, 哚]-2Χ1Ή)-ketone' A 11.33 N'N_i formazan [ί2::嗣气_2i-dihydrospiro [furo[2,3-g][l,4] Dioxanthene·8 3,丨Γ(2Ή)-yl)methyl]furanylcarboxamide A 143924-sp-20091127-6 -1039 - 201020257

Example No. Compound name Ki(^M) 11.64 (3S)-6-Methoxy-5-mercapto-indole-[(4-methylhexahydrop-roughing_ι_yl)methyl]spiro[1-benzene And furan-3,3'-throindole]-2·(ΓΗ)-ketohydrochloride B 11.66 (3S)-r-[(2R)-E9 Hydrofuran-2-ylmethyl]_5,6_2 Hydrogen snail [benzo[l,2-b:5,4-b']difuran-3,3,-啕哚]-2'(1Ή)-one B 11.67 (3R)-l'-[(2R )-ra Hydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-峋哚]-2' (1Ή)-keto B 11.69 (3S)-r-[(2S)-tetrahydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[l,2-b: 5,4-b·] Difuran-3,3·-吲哚]-2"(ΓΗ)-keto B 11.85 6-(5-fluorenyl-1,2,4-indanoxazol-3-yl)-indole-indolepyridinium -2-ylmercapto) spiro[1-benzofuran-3,3,-吲哚]-2,(1Ή)-one B 16 4'_[6-(didecylamino)> -yl H4(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,] dipyridyl-3,3'-吲嗓]-2'(1Ή)-ketone B 16.6 4 -(4-phenoxyphenyl)_i'_[(2R)_tetrahydrocyl-2-ylmethyl]-5,6-dihydrospiro [Benzo[^7:5,4-b,]difuran-3,3·-啕哚]-2'(1Ή)-net A 16.7 4'-[4-(2-methyl Oxy)phenyl]_r_[(2R)_tetrahydrofuran-2, fluorenyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b'] dipyran-3 ,3'-吲嗓]-2'(1Ή)-ketone A 16.9 4'-(4-methoxyphenylhydrofuran-2-ylmethyl 5,6-dihydrospiro[benzo[1,2-7 :5,4-b']dipyran-3,3'-吲哚]-2'(ΓΗ)-ketone A 16.10 4'-Bite 2,5-yl-1,-[(condition)_tetrahydrofuran_ 2_ylmercapto]_5,6_di-argon-[benzo[l,2-b:5,4-b']dioxin-3,3'-^丨哚]-2'(ΓΗ)-ketone B 16.80 1'-Methyl-4- phenoxy 2,3_dihydrospiro[吱,[2,3-g] [i,4]benzodioxene-8,3'-吲哚]-2,(1Ή)-ketone A 143924-sp-20091127-6

(S-1040. 201020257 Biological Example 3 Tail flick latency test induced by analgesic heat caused by a sodium channel blocker In this test, by administering the compound of the present invention to the analgesic effect, The heat-induced tail flick is observed in the mouse. This = source, which includes a projection lamp, has a beam of light that is focused and directed at a point on the tail of the milk. The tail flicks the incubation period, which is evaluated before the drug and responds Harmful thermal stimuli, meaning the response time from the application of the light-spot on the back side surface to the tail flick, measured and recorded at 4〇, 8〇, 120 and 16〇 minutes. In the first part, 65 animals received an assessment of the baseline tail flick latency, once a day, after two text days. Then, the animals were randomly assigned to one of the n different treatment groups, including the vehicle. Control the parental, morphine control group and 9 compounds, administered intramuscularly at 30 mg / kg. After dose administration, closely monitor the animal's signs of toxicity, including tremor or seizures, hyperactivity, shallow lying, Rapid or suppressed breathing and failure to comb. The optimum induction time for each compound is determined by regression analysis. The analgesic activity of the test compound is expressed as the percentage of the maximum possible effect (% ΜΡΕ), and the following formula is used. Calculation: % ΜΡΕ a jgjji incubation period - pre-dose incubation period (ίο sec) - before taking the drug 丨 ^ 1 〇〇 % 其中 义 = = = = = = = = = = = = = = = = 接受 接受 接受 接受 接受 接受 接受 接受 尾 尾 尾 尾 尾 尾 尾 尾 尾Latent time spent 143924-sp-20093127-6 1041 201020257 6-methoxy-5-mercapto-r-[(2R)-tetrahydrofuran-2-ylindenyl] snail 3,3·-,?丨哚]-2'(1Ή)-ketone; 6-methoxy-5-mercapto-oxime-0-biti-2-ylindoleyl]spiro[1_benzofuran_ 3,3,_巧丨哚]_ 2,(1Ή)-ketone; 6-decyloxy-5-methyl-oxime-(tetrahydro-2Η-喊喃-2-ylindenyl) snail []L Benzo-pyran-3,3'-吲哚]-2·(1Ή)-one; 5-fluoro-6-methoxy-indole-(tetrahydro-2Η-喊.南-2-ylmethyl )Spiral []L benzophenone biting -3南-3,3·-吲哚]-2·(1Ή)-one; 5-fluoro-6-methoxy-Γ-(竹b bit-2-yl Snail [ι_benzopyran 4丨嗓]_ 2'(1Ή)-one; 5-fluoro-6-methoxy-r-[(2R)-tetrahydrofuran-2-ylindenyl] spirobenzoindole-3,3'-啕哚]-2'(1Ή)-one; Γ -octyl-5-1-yl-6-methoxyspiro[1-benzopyrene-3,3^5丨嗓]_2, (1, im-ketone; 6-methoxy-l'-[ (2R)-tetrahydrofuran-2-ylindenyl]spiro[lbenzofuran_3,3,_w 哚]-2'(1Ή)-one; 6-bromo-1'-[(2R)-iz9 hydrogen Furan-2-ylindenyl]spiro[ι_benzofuran_3,3,_ρ?丨哚]-2Χ1Ή)-one; 6-fluoro-5-nonyloxy-1'-{[5-( Trifluoromethane-based ketone-2-yl] fluorenyl sulfonium benzophenone-3,3'-吲哚]-2'(1Ή)-one; 5.6-dimercapto-1'-(four Hydrogen-211-piperid-2-ylmethyl) snail [1_benzofuran_3,3,_11 丨哚 丨哚]-2'(1Ή)-one; 5.6- —曱基_(四风_2Η -ρ辰喃-4-ylindolyl) snail [1_benzopyrano- 3,3,_j^丨哚]-Τ(ΓΗ)-ketone; 5.6-dimethyl-oxime-0-pyridine- 2-based fluorenyl) snail [ι_benzofuran_3,3,_ρ?丨哚]_2, (1ή) 143924-sp-20091127-1 -106 > 201020257 The incubation period of the drug = before receiving the drug, The tail flicks away from the heat source of the beta 'the latency of the individual animals. Deadline (ίο sec) = the highest exposure to the heat source. Acute pain (formalin test) The formalin test was used as an animal model of acute pain. In the Fumali test, the system was used to make the animal λ before the experimental day, and the short organic cell test room was 2G minutes #. On the day of the experiment, the animals were randomly injected into the test article. At 30 minutes after administration of the drug, 5 μL of 1% hemoline was injected subcutaneously into the plantar surface of the left hind paw of the rat. Image data acquisition begins immediately after the administration of Formalin and lasts for 9 minutes. The image was taken using the Actimetrix Limelight software, which stores the file in the extension and converts it into ΜρΕ(}_4 encoding. Then, using the behavioral analysis software. Observer 5. Γ (5. 〇版, Noldus Information Technology, Wageningen, The Netherlands) Analyze images. Image analysis is performed by paying attention to animal behavior and classifying each item according to its type and defining the length of the behavior (Dubuisson and Dennis, 1977). The scored behaviors include: (1) normal behavior, (2) No weight placed on the palm of the foot, (3) raise the foot '(4) 舐 / bite or scrape the foot. After the injection of the foot, the care or excessive sputum, bite and scraping, the pain response Both feet are resting on the floor, without significant care of the injected foot, excessive licking, biting or scraping' shows analgesic response or protection from the compound. Analysis of the fumarin test data is based on two factors (1) Percentage maximum possible inhibition (%MPIE) and (2) pain score. %Mpffi is calculated by a series of steps, the first of which will be the abnormal behavior of each animal 14 3924-sp-20091127-6 -1042- 201020257 (Actitude 1, 2, 3) The total length of the media group is obtained by averaging all the scores in the vehicle treatment group. The following calculations are generated per MPIE value for only animals: MPIE (%) = 100 - [(treatment sum / average media value) χ 1〇〇%] The pain score is calculated from the weighted scale described above. Multiply the duration of the behavior by the weighted value (response The severity level is divided by the total length of observation to determine the pain level of each animal. The calculation is expressed as follows: Pain level = [0(T〇) + 1(T1) + 2(T2) + 3 (Τ3)]/(Το + ΤΙ + Τ2 + Τ3) ® Chronic inflammatory pain caused by CFA In this test, tactile sensory abnormalities were assessed with calibrated 2V〇nFrey filaments. After the week, 15 〇 microliters "completely raped eund's adjuvant " (CFA) emulsion (CFA was suspended in oil / brine (1:1) emulsion at a concentration of 0.5 mg / ml), Under the anesthesia of is〇flurane, it is injected subcutaneously into the plantar surface of the left hind paw of the rat. Recovery, and one week after CFA administration, the baseline thermal and mechanical nociceptive lows of all animals were evaluated. On the day before the start of the experiment, all animals were accustomed to the experimental equipment for 20 minutes. The test and control objects were administered to the animals and At the time limit after drug administration, the lower limit of the nociceptive was measured to determine the analgesia for each of the six available therapeutic drugs (4). The time points used were predetermined to show the highest analgesic effect on each test compound. The lower limit of thermal sensation in animals was assessed using the Hargreaves test. The animal is placed in a colloidal glass enclosure and placed on a raised glass platform with a heating unit. The glass platform is tested for all tests. The temperature is controlled by 143924 and the temperature is 143,924. At the temperature. After placement in the enclosure, the animals were allowed to acclimate for 20 minutes until all exploration activities were stopped. A Type 226 Foot/Tail Stimulator Analgesic Meter (IITC, Woodland Hills, CA) was used to apply a radiant heat beam from beneath the glass platform to the plantar surface of the hind paw. During all test attempts, the idling intensity and activity intensity of the heat source were individually set at i and 45, and a 20 second cut-off time was employed to prevent tissue damage. The animal's low response to tactile stimuli was measured by the test using a Model 2290 Electmvonfrey anesthesia (IITC Life Sciences, w〇〇dland Hms, CA). The animals are placed in an elevated gel glass enclosure and placed over the surface of the loach web. After 10 minutes of compliance, the pre-calibrated v〇n Frey hair was applied perpendicularly to the plantar surface of the animal's two soles, starting from 0.1 gram of hair in ascending order, with sufficient force to cause the hair to face slightly to the sole of the foot. bending. The test is continued until it is determined that the hair with the lowest force causes a rapid flick of the paw' or when the cut-off force is about 2 gram. This cut-off force is used because it represents about 10% of the animal's body weight and is used to prevent the entire limb from rising due to the use of stiffer hair, which will alter the nature of the stimulus. Post-operative mode of sensation injury In this mode, the hyperalgesia caused by the plantar incision in the sole of the foot is measured by applying an increased tactile stimulus to the foot until the animal retracts from the applied stimulus. Its sole. When the animal is anesthetized under 35% isofluorane (which is transmitted via the nose cone), the 1 解剖 anatomical blade is used in the plantar aspect of the left hind paw, resulting in a 1 cm longitudinal incision through the skin and The fascia begins 0.5 cm from the proximal edge of the heel and extends toward the 143924-sp-20091127-6 201020257 toe. After cutting, use a 2, 3-0 sterilizing silk suture to place the skin nearby. Cover the affected area with polysporin and Betadine. Return the animal to its original cage for overnight recovery. With regard to both the surgical (ipsilateral) and non-surgical (contralateral) feet, the low limit of retraction of the animal's tactile stimulus can be measured using the Model 2290 Electrocrofrey anesthesia (IITC Life Sciences, Woodland Hills, CA). The animals are placed in an elevated gel glass enclosure and placed over the surface of the loach web. After accommodating for at least 10 minutes, the pre-calibrated v〇nFrey hair is applied vertically to the sole surface of the animal's two feet, in ascending order, starting from 1 gram of hair, with sufficient force to cause the hair to face the palm Slightly bend and continue testing until the hair is measured to cause a rapid flick of the foot with minimal force, or when a cut-off force of approximately 2 grams is reached. This cut-off force is used because it represents about ι% of the animal's body weight and is used to prevent an increase in the entire limb due to the use of stiffer hair' which will alter the nature of the stimulus. Neuropathogenic pain pattern; chronic contracture injury φ In short, in the thigh level of the animal's left hind foot, using the No. 10 dissection blade' through the skin and fascia, resulting in an incision of approximately 3 cm. Dissect the biceps through the biceps, expose the left sciatic nerve, and carefully remove the scale. Four loose lines were placed along the sciatic nerve to make the material non-degradable. The sterilized silk sutures were knotted at intervals of (1) mm. When viewed under anatomical microscopy at 4x magnification, the tension of the loose binding line is sufficiently tight to cause a slight contraction of the sciatic nerve. In the simulated animals, the left sciatic nerve was exposed' without further processing. The antibacterial ointment is applied directly to the wound and the sterilized suture is used to close the muscle. 143924-sp-20091127-6 -1045-201020257 Betadine was applied to the muscle and its surroundings. The skin was then closed with a surgical clip. Animals responded to low limits on tactile stimuli using the Model 2290 Electromvonfrey Anesthesia (IITC Life Sciences, Woodland Hills, CA). The animals are placed in an elevated gel glass enclosure and placed over the surface of the loach web. After 10 minutes of compliance, the pre-calibrated ν〇η Frey hair was applied perpendicularly to the sole surface of the animal's two feet, starting in the ascending order, starting from 1 gram of hair, with sufficient force to cause the hair to face the palm of the foot Slightly bent. Continue testing until the hair is measured to cause a rapid flick of the palm with minimal force, or when a cut-off force of approximately 20 grams is reached. This cut-off force is used because it represents approximately the animal's body weight and is used to prevent the entire limb from rising due to the use of stiffer hair. This will alter the nature of the stimulus. The lower limit of thermal nociception in animals was assessed using the Hai*greaves test. After the tactile low limit metric, the animal is placed in a colloidal glass enclosure disposed over a raised glass platform having a heating unit. The glass platform was thermostatically controlled at approximately 24 to 26 temperatures for all test attempts. After the woman is placed in the enclosure, the animal is allowed to acclimate for 10 minutes until all ® probing behavior is stopped. Use the Type 226 Plantar/Tail Stimulator Painometer to print W〇〇dland Touch, CA)' to apply a radiant heat beam from beneath the glass platform to the plantar surface of the hindfoot' palm. During all test attempts, the idling intensity of the heat source is indistinguishable from the intensity of the activity, and the cut-off time is used to prevent tissue damage. Neuropathogenic pain pattern: spinal nerve ligation Spinal nerve ligation (SNL) neuropathic pain pattern as a neuropathy 143924-sp-20091127-6

-1046- 201020257 The use of the original pain animal (meaning the big white 曰 曰 )) model. In the SNL test, the spinal nerve L5 and the L6 lumbosacral root a are tightly ligated to cause nerve damage, which causes mechanical hyperalgesia, and the spread of the sputum is also mechanically abnormal and hyperallergenic. The development of the surgical department was performed two weeks before the test, so that the pain state was developed in the animal. Several ridged nerve ligation variants are used to characterize the analgesic properties of the compounds of the invention. (1) L5 spinal nerve ligation; (2) L5 and L6 spinal nerve ligation; ❹ (3) L5 spinal nerve ligation and cross-section; (4) L5 and L6 spinal nerve ligation and cross-section; or (3) L4 spinal nerve stimulation And use the above (1) (any one. When the animal is anesthetized under the 35% 4 gas-fired (four) position (10) transmitted through the nose cone, use a scalpel No. 10 in the skin just to the side of the dorsal midline' A longitudinal incision of approximately 2.5 cm was made, and the level of the iliac ridge was used as the midpoint of the incision. After the incision, the isoflurane was adjusted to the maintenance level (10) _ ❹ 2 · 5%). At the mid-sacral area, the incision is made with a scalpel and the blade is slid along the side of the spine (in the sagittal plane) until the blade hits the tibia. The tip of the scissors is introduced through the incision, and the muscles are removed from (4) from the ridge (4), and (4) the 2-3 cm spine is exposed. Remove muscles and fascia from the vertebrae to locate the point where the nerves leave the vertebrae. The small glass is placed in the middle of the ridge and the nerve is gently raised from the surrounding tissue. Once the vertebral auditory nerve has been isolated, a small length of non-degradable 6 〇 sterilized wire wrapped around the tip of the ball glass twice, and sent back to the nerve. Then, the spinal nerves are firmly ligated by knotting, ensuring that the nerves bulge on the two sides of the binding line 143924-sp-20091127-6 -1047- 201020257. This procedure can be repeated as needed. In some animals, the w-spinal nerves can be rubbed in small glass (up to 2G times) to maximize the development of neuropathic pain. Apply the anti-bacterial ointment directly to the incision' and use a sterilized suture to apply the muscle m-bedadine (touch (4) to the muscle and its surroundings' followed by surgically fixed fibers or sterile non-absorbable monofilament 5-0 nylon The suture is used to close the skin. The analgesic effect produced by topical administration of the compound of the invention to the animal can then be found by measuring the animal's retraction of the paw of the mechanical tactile stimulus. These can be used as follows a mechanical paresthesia procedure or a mechanical hyperalgesia procedure metric. The appropriate baseline metric is established by either method, after which the topical formulation of the compound of the invention is applied to the ipsilateral ankle and foot. Animals were placed in plastic tunnels for 15 minutes to prevent them from being treated and the compounds removed. The animals were placed in acrylic before testing the ipsilateral foot by any of the methods described below. In the enclosure, after 15 minutes, and the response was recorded at 5, 1 and 2 hours after treatment. A. Mechanical sensory abnormality method For the operation and control of the two animals, manually calibrated v〇n support fibrils can be used approximately 14 days after surgery, as measured below. The animals are placed in a raised plastic glass enclosure, set in On the surface of the wire mesh. Allow the animal to adapt to the environment for 2〇3〇. Apply the pre-calibrated Von Frcy hair vertically to the plantar surface of the ipsilateral foot of the animal' starting from 2.0 grams of hair with sufficient force to cause hair pair The curve of the foot is slightly curved to establish a baseline metric. The stimulus is presented in a continuous manner 143924-sp-20091127-6 -1048- (S) 201020257, in ascending or descending order, I to the first change in the discovery response So far, four other responses were recorded, providing a total of six responses. The six responses input in grams are measured by chaplan, s R et al. _ chest; 53(1): 55_63, and the contraction is calculated. Back-valve value. This constitutes a mechanical sensory outlier. 机械.Mechanical hyperalgesia method Animals respond to tactile stimuli Thresholds are measured using a fiber type Electrov〇nfrey anesthesia meter (iitc life sciences, woodlandHms CA). Place the animal in an elevated colloidal glass enclosure. After 15 minutes of placement in the closure on the surface of the wire mesh, the rey hair is applied vertically to the plantar surface of the ipsilateral hind paw of the animal. Force, measured in grams, to induce a brittle response to the foot. This response is shown by the retraction of the pain stimulus, which constitutes the force effect, point, and data. The data is expressed as a percentage change from the baseline threshold, measured in grams. Arrhythmia test caused by φ aconitine~ The anti-arrhythmia activity of the compound of the present invention is confirmed by the following test: Arrhythmia is administered intravenously to aconitin which has been dissolved in physiological saline (2) · 0 μg / kg) was induced. The test compound was administered intravenously for 5 minutes after the administration of aconitine. The evaluation of anti-rhythm* Qi activity was measured by the time from the administration of aconitine to the external contraction (ES), and from the aconite = technique The time from the time of the drug to the occurrence of ventricular tachycardia (VT). Tracheotomy in rats under anesthesia (2% 1/4 to 1/3) anesthesia' by first establishing an incision in the neck region, then single 143924-sp*20091127 -6 -1049- 201020257 Detach the trachea and create a 2 mm incision to insert the tracheal tube into the trachea 2 cm so that the opening of the tube is just above the mouth. Fix the tube with a suture and connect it to the ventilator. Then, an incision (2.5 cm) was made in the femoral region, and a blunt dissection probe was used to separate the femoral vessels. Two femoral veins were intubated, one for the pentobarbital anesthetic to maintain _2-0.05 ml) A tube for perfusion and injection of drugs and vehicles. Intubate the femoral artery with a blood pressure gel catheter of the transmitter. Connect the ECG lead to the pectoral muscle at the position of the lead 11 (upper right / above the heart - white lead, with the lower left / The 'red wire' below the heart. The wire was fixed with a 10-wire line. All surgical areas were covered with a frying cloth moistened with α9% saline. Saline (1-1.5 ml, 〇 9% solution) was supplied to moisten the post-operative area. Animal ECG Balance with ventilation for at least 3 minutes. Rhythm is induced by infusion of 2 μg/kg/min aconite for 5 minutes. During this period, ECG is recorded and continuously monitored. Compounds of the invention can be used in such test towels. Frequently, in the treatment of rhythm* = the arrhythmia caused by the arrhythmia test: the circadian rhythm of the tooth-tooth model, in the acute cardiac steering and prevention paradigm, p 播播田%丨Μ Has been used to test potential therapeutic agents for human =; arrhythmia both. It can lead to myocardial infarction, the common cause of death from death, and the common cause of mortality. Compounds prevent blood loss caused by pulsatile overspeed The ability of fiber to vibrate is the accepted mode, 143924-sp-20091I27-6

-1050 - 201020257 For the determination of the efficacy of compounds in atrial and ventricular tachycardia and fibrillation in a clinical setting. The anesthesia was first induced by pentobarbital (intra-abdominal) and maintained by intravenous bolus perfusion. The male SD rat has a gas S inserted through the cannula, and artificial ventilation is performed inside the air, at a stroke volume of cc/kg, 60 beats/min. The right femoral artery and vein were intubated with pE5 fistula, and individual mean arterial blood pressure (MAP) was recorded for intravenous administration with the compound. The chest between the 4th and 5th ribs will be opened to create a 15 male mouth so that the heart is visible. Place the rats on the notch platform and hook the metal restraint to the rib cage to open the chest. A suture needle is used to penetrate the ventricle just below the raised anterior chamber and is happy in a downward diagonal direction so that a >30% to <5%% occlusion zone (〇z) will be obtained. The exit position is lower than ~5 cm below where the aorta is connected to the left ventricle. The suture is tightened so that a loose coil (occlusion) is formed around the arterial branch. The chest is then closed with the end of the occlusion that can enter the outside of the chest. Place the electrode in the π position of the wire (right anterior chamber to the top) for ECG measurement, as described below. Insert one electrode into the right forefoot and the other electrode into the left hind paw. Body temperature, MAP, ECG, and heart rate were continuously recorded throughout the experiment. Once the key parameters have been stabilized, a μ2 minute record is taken to establish a baseline value. Once the baseline value is established, the perfusion of the compound or control substance is initiated. After 5 minutes of perfusion of the compound or control, the suture was tensioned to ligature the LCA and cause septicemia in the left ventricle. After ligation, key parameters were continuously recorded for 20 minutes unless MAP reached a criticality of 2〇_3〇mm 143924-sp-20091127-6 -1051 - 201020257 ketone; 5-fluoro-6-methoxy-Γ-(four Hydrogen-2H-piperazin-4-ylmethyl)spiro[1-benzofuran-3,3'-indole]-2'(1Ή)-one; 5-fluoro-6-methoxy-1 '-{[5-(Trifluoromethyl)pyran-2-yl]methyl}spiro[1-benzofuran-3,3'-吲哚]-2'(1Ή)-one; 5.6- Fluorin-Γ-〇 咬 -3--3-yl fluorenyl) spiro[1-benzopyran-3,3W丨嗓]-2'(1Ή)-one;

5.6-Difluoro-indole-{[5-$fluoroindolyl)pyran-2-yl]indenyl}spiro[1-benzofuran_3,3L 啕哚]-2'(1Ή)-one; 6_曱oxy_1'_(pyridin-2-ylindenyl)spiro[1-benzofuran-3,3'-啕哚]-2,(rH)-one; 6-decyloxy-oxime -(pyridin-3-ylindenyl)spiro[1-benzofuran_3,3,_吲哚]_2, (i,h)-one; 6-methoxy-indole-(tetrahydro-2H- Piperazin-4-ylindenyl)spiro[1_benzofuran_3,3,吲哚]-2'(1Ή)-one; 6-methoxy-oxime-(tetrahydro-2-indole-pyran) 2-ylmethyl)spiro[μbenzofuran_3,3,_吲哚]-2'(1Ή)-one; 6-amino _r_[(2R)_whydrofuran-2-ylmethyl] Snail [1-Bist and furan _3,3,_吲• 〃 ]]-2'(1Ή)-嗣; Ν-{2,-keto-1,-[_-tetrahydromethane I fluorenyl ] 4,, 2, _ dihydrospiro [I benzofurazan-3, 3.丨哚]-6-yl} decane decylamine; 6-trans-yl-hydrazine-(3-methylbutyl) snail [1_benzofuran _3,3W|哚]2, (called net; 6-Hydroxy-indole-(3-mercaptobutyl)-5-(trifluoroethenyl) snail as benzofuran n吲哚]-20Ή)-one; '(3R)-3-[(2,- Ketopropyl-1'-{[5-(trifluoromethyl) succinyl-2-yl]methyldihydrodihydrospirobenzofuran-3,3'-indole]-mercapto) Hydropyrrole citrate third 143924-SP-20091127-1 -107- 201020257

Hg, after at least 3 minutes, in this case, the recording is stopped because the animal will be declared dead and then sacrificed. The compounds of the invention prevent irregular rhythm and maintain near normal MAP and HR ability, are scored and compared to the control group. Biological Example 6 In vivo detection of benign prostatic hyperplasia (BPH) The effectiveness of the compounds of the present invention for the treatment of BPH can be confirmed by the following in vivo assay. The compound of the present invention was orally administered by the dog at an oral dose of between 〇mg/kg and 100 mg/kg for 4 weeks. The control group received a placebo. The animal is sacrificed, the prostate is dissected out, patted to dryness, and then weighed. μ Biological Example 7 In vivo detection of anti-hypercholesterolemia efficacy and anti-atheroma sclerosing agent efficacy The dog has a human-like cardiovascular system that makes them ideally used to study medicines designed to treat cardiovascular disorders. The role of the compound. ❹ The dog is administered orally at a dose ranging from 0 mg/kg to 1 mg/kg for 2 to 4 weeks. After 2 and 4 weeks, the animals were bled "and their serum was collected for total cholesterol analysis and compared to animals taking a separate vehicle (〇 mg/kg). One of the sterols is measured in a clinical laboratory environment. A simple camp luminometer method for quantifying the sensitivity of the most common test sterols in plasma or serum is used frequently. In one test, the steroids 143924-sp-20091127-6 -1052 - 201020257 sterol esters were first hydrolyzed by cholesterol esterase. All cholesterol, whether pre-acetified or in the existing free state in the circulation, is then oxidized by bile fermentation oxidase to its corresponding ketone and hydrogen peroxide. Acetyl _3,7_ hydroxy hydroxy pricking is used as a highly sensitive and stable probe for hydrogen peroxide. Horseradish peroxidase catalyzes the reaction of ADHp with hydrogen peroxide to produce a still fluorescent product, resorafin, which can be monitored using an excitation wavelength of 565 58 毫 nm and an emission wavelength of 585-595 nm. Biological Example 8 In vivo assay for the treatment of scrapie The compound of the present invention can be evaluated for its activity as an antipruritic by an in vivo test using a rodent model. An established mode for inducing pruritus in a peripheral manner is serotonin injection into the posterior region (neck) of the mouth of the hairless rat. Prior to serotonin injection (eg, 2 mg/ml, 50 microliters), the dose of the compound of the invention may be administered systemically or locally to the circular region by the oral, intravenous or intraperitoneal route (eg, 18 mm). After taking the drug, serotonin injection is given in the area where the drug is administered locally. After serotonin injection, animal behavior was monitored by imaging recording for 20 minutes to 1.5 hours, and the number of scratches during this period was compared to vehicle treated animals. Therefore, administration of the compound of the present invention can suppress the seizure caused by serotonin in the rat. Biological Example 9 Cytochrome P450 (CYP450) Inhibition Assay CYP450 (CYP) is the name for the enzyme supergroup. Each ethnic group consists of one or more subpopulations' and each subpopulation comprises one or more specific CYp iso 143924-sp-20091127-6 1053 - 201020257 recombinants. The cytochrome P450 (CYP450) inhibition assay is a fluorescence-based assay using CYP isozymes for screening compounds of the invention to determine the extent of inhibition by CYP450 of a particular compound. This test was based on the CYP suppression kit described by the Vivid CYP450 Screening Kit, 2005, Invitrogen, Inc. (Invitrogen, 1600 Faraday Avenue, Carlsbad, CA 92008, USA). This assay was designed to evaluate compounds by quantifying the inhibition of the major human CYP450 isozyme involved in hepatic drug metabolism. It is based on the principle that the principle is derived from testing the ability of many pharmacologically active compounds to act as receptors and inhibitors for most of the drug biometabolism enzymes (primarily CYP), or for their interference with the metabolism of existing drugs. effect. The standard method for assessing inhibition of a particular CYP isozyme is to determine the conversion of the probe (Table 4) to its new metabolic product in the presence and absence of an effective inhibitor. The quantification of the metabolites is achieved by HPLC or by the detection of bioaccumulation into a fluorescent product (fluorescence detection). Four CYP isozymes were studied: CYP3A4, 2C9, 2C19 and 2D6. In particular, CYP3A4 has been shown to be one of the most important isozymes involved in the metabolism of drugs in the body (see http://medicine.iupui.edu/flockhart/table.htm). A drug that inhibits a specific CYP isozyme can reduce the metabolism of the drug' and increase the serum concentration of the drug as a charge for the isozyme. The CYP3A4 data reported below can be used to predict possible clinical drug-drug interactions for a particular compound. 143924-SP-20091127-6 • 1054 - 201020257 Table 4. CYP450 isoenzyme (CYP) and acceptor CYP used in the head of the word structure name 3A4 BOMCC 7-(芊 methoxy methoxy)-3-cyanide Coumarin 2C19 EOMCC 7-(ethoxymethoxy)-3-cyanocoumarin 2C9 BOMF (benzyloxymethoxy) fluorescein 2D6 MOBFC 7-(4-methoxy oxime )-4-trifluoromethyl glucoside

Table 5. CYP450 isozyme inhibitor isozyme inhibitor concentration in 10 assays % inhibition in 10 assays IC5〇(nM) 3A4 Brewing I Kang. Sit 0.1 – 50 +/- 10% 88 +/-30 nM 2C9 Sulfapyrazole 0.420 /M 50 +/- 15% 345 +/-20 nM 2C19 Ketocon ° 7.62 (M 65 +/- 10% 3132 +/- 680 nM 2D6 quinidine 0.0137 fM 55 +/- 15% 15 +/- 5 nM Table 6. Term name definition regeneration system (RS) ΙΟΟχ contains 333 mM glucose-6-phosphate and 40 U/ml glucose - 6-phosphate dehydrogenase in 100 mM potassium phosphate buffer (pH 8.0). Baculovirus microsomes (Bac) are made from microsomes of insect cells that are involved in human CYP isozymes (1 specific P450 content) baculovirus infection with cDNA of rabbit NADPH reductase. NADP+ Nicotine guanamine adenine dinucleotide phosphate, at 10 times in potassium phosphate buffer (100 mM, pH 8.0). NADP+ is converted to NADPH by a regeneration system to initiate the CYP450 reaction. The reaction buffer contains 100 or 200 mM potassium phosphate buffer. The premix contains reaction buffer, RS, Bac. Individually prepared for each isozyme. The mixture contains reaction buffer and substrate (BOMCC, EOMCC, 143924-SD-20091127-6 • 1055 - 201020257 BOMF or MOBFC) NADP+. Individually prepared for each isozyme. This test can be used for single concentration screening or for IC50. In a single concentration screening test, the final concentration of the test compound is 1 〇 from Μ. In the assay, the IC50 can be replicated in triplicate using a 3, 6 or 12-point curve, using a selected initial concentration that is continuously diluted. Preparation Stage: In the preparation stage, the test compound, control (acetonitrile) ACN) or diterpenoid (DMSO) and no baculovirus microsomes and known inhibitors (Table 5) were diluted in water to 10% ACN or DMSO at appropriate concentrations. Premix and substrate mixture Also prepared according to the kit instructions. The premix consists of P450 baculovirus microsomes, regeneration system (RS) and Vivid® CYP450 reaction buffer. The matrix is made of Vivid®, NADP+ and Vivid® CYP450. Composition of reaction buffer. Detection phase: In the detection phase, add 30 μl of water to each well of the 96-well test plate. Then, add the test compound, negative control or known inhibitor to the water stock solution. 10 microliters 10% AC N or DMSO to the designated well, according to the plane of the test plate. The third step was to add 50 microliters of premix solution to each working well (but for the absence of baculovirus microsomal control wells, 50 microliters of buffer was added instead). Next, the test panel was preheated in the dark for 20 minutes at ambient temperature. When preheating was completed, 10 microliters of the substrate-mixed solution was added to each working well (containing a baculovirus-free microsomal control well). This will result in a final 1% ACN or DMSO concentration. Place the assay plate immediately in the PolarStar board reader to read the initial fluorescence. The assay plate was again incubated in the dark at ambient temperature 143924-SO-20091127-6 1056 · 201020257 degrees for 20, 30 or 60 minutes depending on the reaction time of the isozyme (Table 7). Ten microliters of termination reagent was added to each working well and the final fluorescence was read. Table 7: Isozyme reaction time and termination reagent isozyme reaction time (minutes) Termination reagent concentration 3Α4 20 10 //Μ ketone Kang 2C19 20 30 / ketone Kang Jun 2C9 30 10 / sulfonamide benzopyrazole 2D6 60 1 //ΜQuinidine data analysis: The difference between the initial and final fluorescence readings was used to calculate the percent inhibition. ACN or DMSO readings indicate 0% inhibition, while no baculovirus microparticle readings indicate 100% inhibition. The percent inhibition by this compound or known inhibitor was calculated on the basis of a comparison of the solvent (ACN or DMSO) control group with the baculovirus-free microsomal control group. To minimize any fluorescent compound or background effects, the initial relative fluorescence unit (RFU) is subtracted from the last RFU. Determination of % inhibition of each CYP450 isozyme with respect to each compound or control: Compound (RFU last-initial)-DMSO control (RFU last-initial) % inhibition = -X100 No Bac (RFU last-initial)-DMSO control Group (RFU Final - Initial) Representative compounds of the present invention, when tested in the above assays, exhibit a percent inhibition of the CYP3A4 isozyme as set forth below in Table 8, where ΠΑ" means at 10 //M Lower than 50% inhibition percentage, and "B" refers to the inhibition percentage number greater than 50% at 143924-sp-20091127-6 -1057 - 201020257 provided in Table 8 for example 10 /zM corresponding to Examples of this article: Table 8

Example No. Compound name CYP3A4 % inhibition 1 2-methylspiro[吱,[2,3-f][l, 哚]-2'(1Ή)-ketone' A 1.1 14(6-mercaptopurine-bit 2-yl) fluorenyl]-2,3-dihydroanthracene "唼咗[2,3-g][l,4]benzodioxolene _8 33⁄4% lost 哚]-2' (1Ή )-keto B 1.2 Γ-7-pyridin-3-ylmethyl)-2,3-dihydrospiro[吱,[2,3_g] [1,4]benzodioxanthene]丨嗓-2 ,(ιή)-_ A 1.3 1 _{[2,5-monodecyl-1-(1-methylethyl)-1Η-ρ ratio _3_ yl]methyl} snail [吱 并[2 ,3-f][l,3]benzodioxanthene-73'-吲哚]-2'(1Ή)-keto B 1.4 5-(benzyloxy)-indole-[(5-chloro) -2-nonyl)indenyl]spiro[μ benzofuran-3,3'-吲哚]-(1 鲷-鲷B 1.5 7'-bromo snail [吱 并[2,3-f ][l,3]benzodioxanthene-7,3'-吲哚]-2·(1Ή)-keto B 1.6 Γ-[(3-isopropylisoxazole-5-yl)indole Snail [吱,[2,3-f][l,3]benzodioxene _7,3'-吲哚]-2,(1Ή), B 1.7 Γ-[(4- Bromo-2-indolyl)methyl]spiro[吱,[2,3_f][1,3]benzodioxolene-7,3·-峋哚]-2,(1Ή)- Ketone B 1.8 Γ-(1-benzofuran-2-ylindenyl) snail [biting and arranging [2] ,3-f] [i,3]benzodioxolene-7,3'-啕哚]-2'(1Ή)-keto B 1.9 1'-{[2-methyl-5-(three Fluoromethyl)-l,3-oxazol-4-yl]methyl} snail [吱,[2,3-f][l,3]benzodioxanthene-7,3'-吲哚]-2,(l,H)-keto B 1.10 (3R)-5,6-di-spiro[benzo[7:5,4-b']difuran-3,3'-吲哚] -2'(1Ή)-ketone A 143924-sp-20091127-6 • 1058 · 201020257

Example No. Compound name CYP3MiT % inhibition 1.10 (3S)-5,6-dihydrospiro[benzo[ub:5,4-b,]difuran-3,3'-蚓哚]-2'(ΓΗ)- Ketone B 1.11 (R)-3,7-Dihydro-2Η-spiro [benzofuro[5,6-b][l,4]dioxanthene-8,3,-dihydroanthracene] -2,-keto A 1.11 (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-吲哚] -2,(1Ή)-ketone A 1.12 (8S)-r-{[3-^fluoromethyl)acridine_2_yl]methyl b 2,3_dihydrospiro[吱,[2,3 -g][l,4]benzodioxanthene-8,3'-吲哚]_2'(1Ή)-ketone A 1.13 (8S)-l'-[(5-hydroxypyridin-2-yl) ) fluorenyl]-2,3-dihydrospichrano[2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-2'(1Ή)- Ketone A 1.14 14(5-Bromopyridin-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-§][1,4]benzodioxanthene- 8,3,-吲哚]-2'(1Ή)-ketone B 1.15 Γ-{[5-(4-Phenylphenyl)-2-(trifluoromethyl)indol-3-yl]fluorenyl} Snail [吱,[2,3-f][l,3] stupid and dioxolene-7,3'-吲哚]-2'(1Ή)-ketone A 1.16 gas-based-1-methyl -3-(trifluoromethyl)-indole-pyrazol-4-yl]methyl} snail [pyrano[2,3-f][l,3]benzodiox Alkene-7,3,-吲哚]-2,(1Ή)-remaining B 1.17 Γ-(5-methoxypyridin-3-yl)spiro[吱,[2,3-f][l,3 Benzodioxanthene-7,3'-峋哚]-2·(1Ή)-keto B 2.3 1 -(dihydromethane)-5,6-dimethylspiro[1-benzopyrene南南-3,3'-嘀哚]-2·(ΓΗ)-ketone A 2.6 methoxyindolyl-3-methylspib-propan [1,2] benzisoxazole-5, 3'-,?丨哚]-2·(1Ή)-keto B 2.9 1 -(diphenylfluorenyl)-5-fluorospiro[1-benzopyrano_3,3'-<»5丨哚]-2'(1Ή)-ketone A 2.11 Γ-(diphenylfluorenyl)-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene Alkene-8,3'-吲嗓]-2·(1Ή)-ketone A 143924-sp-20091127-6 -1059- 201020257

Example No. Compound name CYP3A4% inhibition 2.14 Γ_(二曱曱基)-2-曱yl snail [吱,[2,3-f][l,3]Benzene*°°Sit-7,3'- β卜朵]-2'(1Ή)-ketone A 2.16 Γ-(diphenylfluorenyl)-3-indolyl snail [bito-and-[2,3-f][i,3]benzoxazole-7 ,3·-啕哚]-2,2,(1Ή,3Η)-dione A 2.22 6-Bromo-indole-((5-(trifluoromethyl)pyranyl)methyl)-2Η-snail [benzofuran-3,3'-dihydroanthracene]-21-one B 2.23 5-bromo-indole-((5-(trifluoromethyl)pyran-2-yl)indolyl)-2Η -Spirulina [benzofuran-3,3'-dihydroindole]-2·-one B 2.24 6'-Isoamyl-3,7-dihydro-2Η-snail [stupid and astringent [5, 6-b] [1,4]dioxene terpene-8,8'-p-azolo[5,4-e]吲哚]-7'(6Ή)-_ B 2.25 6-((5- (trifluoromethyl) acetophen-2-yl)methyl)-2,3,5·,6'-tetrahydro-2-indole-spiro[[1,4]dioxoisenene[2,3- fH丨哚-8,3'-benzofuro[6,5-b]furan]-7(6H)-one B 2.26 6-(((R)-w-hydrofuran-2-yl)indolyl) -2,3,5,6,-tetrahydro-2-indole-spiro[[1,4]dioxolynene[2,3-f]indole-8,3·-benzofuran[6 ,5-b]furan]-7(6Η)-ketone A 2.27 6-((5-(Trifluoromethyl)- ran-2-yl)methyl)- 2,3,3,,7,-tetrahydro-2-indole-spiro[[1,4]dioxolynene[2,3-η吲哚-8,8'-benzofuran[5,6 -b][l,4]dioxolene]-7(6H)-one B 2.28 1-indolyl-1·-{[5-(trifluoromethyl) olyl-2-yl]methyl Ι-Μ-dihydro-1H-spiro [Miso-[3,2-g][l,4]benzoindole-8,3^ 哚]-2'(1Ή)-keto hydrochloride B 2.29 1-decyl-l'-[(2R),hydrofuran-2-ylindenyl]-2,3-dihydro-1Η-spiro[吱,[3,2-g][l,4] Benzopyrene -8,3.丨哚]]-2'(1Ή)-ketohydrochloride A 2.30 4-mercapto-14(2R)-tetrahydrofuran-2-ylindenyl]-3,4-dihydro-2-indole-spiro [2,3-g][l,4]benzoindole-8,3,5丨哚]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1060- 201020257 Instance No. Compound Name CYP3A4 % inhibition of 2.31 l'-[(2R)-izg hydroquinone-2-ylindenyl]-4H-spiro[吱,[3,2-g][l,3]benzodioxanthene _6,3·-钊哚]-2'(ΓΗ)-ketooxime 2.34 2,2-Dioxo-indole-{[5-(trifluoromethyl)anthracene. Nan_2-yl]methyl}-spiro-[2,3-f][l,3]benzodioxol-7,3·-啕哚]-2·(1Ή)-one Β 2.35 2,2-di 1 -Γ-{[5-(trifluoromethyl) ρ 口 南 _2 _2 _2 南 南 南 南 南 南 南 南 南 南 南 2 2 2 2 2 2 2 2 2 2 2 And dioxolene-7,3·-吲哚]-2'(1Ή)-ketooxime 2.36 2,2-digas-Γ-{[3-(trifluoromethyl)p-precipitate_2_ Snail [furan[2,3-f][l,3]benzodioxolene-7,3·-叼丨嗓]-2,(1Ή)-ketone A 2.38 3Μ4- Methoxymethyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,indole-pyrrolo[3,2-f]quinoline] -2'(3Ή)-keto B 2.39 6-Hydroxy-indole-(4-methoxyindenyl)_2|·keto-indenyl, 2·_dihydrospiro[1-benzofuran-3,3' -啕哚]-5-carbonitrile B 2.40 6-fluoro-indenyl-(4-indolyl)-2'-keto-indole, 2'-dihydrospiro[1-benzofuran-3 ,3'-啕哚]-5-carbonitrile B 2.41 Γ-(4-methoxybenzyl)-3-methylspiro[吱,[2,3-f] [1,2] benziso Carbazole-7,3'-啕哚]-2'(1Ή)-keto B 2.45 Γ-(4-fluorophenyl)-2,3-dihydrospiro[吱,[2,3-g][ l,4] benzodioxanthene-8,3·-吲哚]-2·(1Ή)-steel A 2.49 5'-molystyl-Γ-〇» than bite-2-yl fluorenyl) -2,3- Hydrogen snail [biting and [2,3-g][l,4]benzodioxanthene_8,3'_啕哚]-2'αΉ)-ketooxime 2.50 2·-keto-1 ·-(Pyridin-2-ylmethyl)-1·,2,2,,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 ,3·-哚哚]-5'-carbonitrile A 2.53 Γ-methyl-2'-keto-1',2,2',3-tetrahydrospiro[吱,[2,3-g] [1,4] benzodioxanthene-8,3·-峋哚]-4'-carboxylic acid phenyl ester 143 143924-sp-20091127-6 -1061 - 201020257

6-[(3R)-tetrahydropbilo-3-ylamino]-Γ-{[5-(trimethylsulfonyl)pyridin-2-yl]methylj snail[1-benzofuran -3,3'-啕哚]-2'(1坶-keto; 6-hydroxy-l'-[(2R)-rahydrofuran-2-ylmethyl]spiro[μbenzofuran·33,_ρ丨哚]-2·α·Η)-ketone; 6-(1-mercaptoethoxy)-l'-[(2R)-tetrahydrofuran-2-ylmethyl] snail [ι_benzofuran -3,3'-呻哚]-2\1Ή)-ketone; (3S)-3-({2'-keto-l'-[(2R)-tetrahydrofuran-2-ylindenyl]-ΐ' , 2,-dihydrospiro[丨_benzopyran-3,3'-吲哚]-6-yl}oxy)tetrahydropyrrole small carboxylic acid third-butyl vinegar; 6-[(3S)- Tetrahydropbilo-3-yloxy]-l'-[(2R)-tetrazinium-2-ylindolyl] snail [丨 并 呋 呋 -3,3'-吲哚]-2' (1Ή)-ketohydrochloride; (3R)-3-({2'·keto-1:[(2R>tetrahydropurine_2_ylmethylhydrazine, 2·_dihydrospiro[L Benzobite-flavor-3,3 丨嗓]-6-yl}oxy)tetrahydro (j is more than η_1_ _ _ _ _ _ _ _ _ cool; 6-[(3R)-tetrahydropyrrole-3- Alkyloxy group H, _[(2R)_rahydrofuran-2-ylmethyl] snail [丨 吱 吱 -3-3,3'-吲哚]-2'(ΓΗ)-keto hydrochloride; 3-[ (2'-keto-1,-{[5-(trifluoromethyl)pyran-2-yl]methyl}_Γ 2, dihydrospiro^•stupid -3,3-吲哚]-6-yl)oxy]tetrahydropyrrolidine-hydrazine-t-butyl tributyl ester; (10) each methoxy-5-mercapto-_r_[(4-methylhexahydro)峨, well + base) methyl] spiro fi-benzoh-am-3,3'-吲哚]-2'(ΓΗ)-keto hydrochloride; (3R)-6-methoxy-5- Base_r_[(4_methylhexahydro, ratio, well+yl)methyl]spiro[benzopyran-3,3·-吲哚]_2·(ΓΗ)-keto hydrochloride; 6-hydroxyl -Γ-(4-methoxybenzyl>2,-keto-oxime 2,-dihydrospiro[丨benzofuran-3,3,·Θ丨哚]-5-indoleonitrile; snail [ 1- benzofuran-3,3,- 6-fluoromethoxymethoxyl)_2,_cylinder _r,2,-two 143924-sp-20091127-1 -108· 201020257

Example No. Compound name CYP3A4 % inhibition 2.54 Γ-{[Η三气曱基>pyridin-2-yl]fluorenyl}-7,8-dihydrospiro[1,4-dioxopine] 2,3-g][l,3]benzodioxanthene~4,3·-吲哚]-2,(1Ή)-ketone A 2.61 1'-(diphenylmethyl)-5,6 -Difluorospiro[1-benzofuran-3,3,-吲哚]-2'(1Ή)-ketone A 2.63 4',5'-dimethoxy-anthracene {[5-^fluoromethyl) ) 吱 _2 _ _ _ 甲基 甲基 甲基 甲基 & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & & 2 2啕哚]-2'(1Ή)-keto B 2.64 4',7'-dimethoxymethoxyethoxy)ethyl]_ 2,3-dihydrospiro[吱,[2,3- g][l,4]benzodioxanthene-8,3·-吲哚]-2·(1Ή)-ketone A 2.65 6-[2-(2-decyloxyethoxy)ethyl ]_2,2|,3,3,-tetrahydrospiro[1,4-dioxolynene [2,3-fH哚-8,8,-furo[2,3-g][l, 4] benzodioxanthene]-7(6H)-_ A 2.66 6'-(4-decyloxybenzyl)-2,3-dihydrospiro[吱,[2,3-g] [1,4] stupid and dioxin-terephthalene-pyrazolo[5,4-e]吲嗓]-7'(6Ή)-keto B 3 6-methyllacto-5-methylspiro[1-benzene弁 喃 _3,3'-巧丨嗓]_ 2!(1Ή), B 3.1 4'-gas-based-5,6-dihydro snail [Benzo[i,2-b : 5,4-b,]difuran-3,3,-吲哚]-2·(ΓΗ)-one B 3.2 6-Bromospiro[1-benzofuran_ 3,3·-吲哚]-2,(1Ή)-嗣B 3.3 5,6-Dimethylspiro[1-benzofuran_3,3'_啕哚]-2·(1Ή)-ketone B 3.4 5^Fluoro-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3'-thirsty]-2·(1Ή)-keto B 3.5 6'-Fluoro-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3·-呻哚]-2,(1Ή)-_ B 3.6 3-methylspiro[吱,[3,2-f][l,2] benzisoxazole-5,3,-^ 丨哚]-2·(1Ή)-ketone A 3.7 5- Gas-based-6-methoxyspiro[1-benzopyrene _3,3'- 巧丨ρ朵]_ 2,(1Ή), A 143924-sp-20091127-6 -1062- 201020257

Example No. Compound name CYP3A4 % inhibition 3.8 5-Fluoro-spiro[1- benzofuran_3,3,_吲哚]-2,(1Ή)-ketooxime 3.10 2,3_Dihydrospiro [2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-2,(1Ή)-ketone A 3.11 Hydrogen 2Η-spiro [repressed [2, 3-h][l,5]benzodiazepine heptarene-9,3'-W哚]-2,(1Ή)-keto A 3.12 2-methylspiro[吱,[2,3- f][l,3]benzoxazole-7,3W丨哚]-2·(1Ή)-ketone A 3.13 3-methylspiro[吱-benzoxazole _7,3,_啕哚] -2,2·(1Ή,3Η)-dione A 3.14 1-decyl snail [c- ace[3,2-f][l,3]benzoxazole-7,3,-吲哚]- 2,2,(1Η,1Ή)-dione A 3.15 7'-gas-based-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3 '-吲哚]_2'(ΓΗ)-ketone A 3.16 7'-Fluoro-5,6-dihydrospiro[benzo:5,4-b,]difuran-3,3,5 丨哚]- 2'(1·Η)-_ A 3.17 4'-Arsyl-7'-mercapto-5,6-dihydrospiro[benzo[i,2-b : 5,4-b·] dipyran -3X 嗓]-2'(1Ή)-keto B 3.21 6,7_Dihydro-5Η-spiro[吱,[3,2-g] acetylene-3,3W| 哚]-2'(ΓΗ) -ketone A 3.22 1-methyl-1Η-snail [吱,[3,2^(^4]benzoindole-8,3·-吲哚]-2,2Χ1Ή ,3Η)-dione A 3.23 4-methyl-4,7-dihydrospiro[benzofuro[5 6_b][14]噚耕-8,3'-dihydroanthracene]_2,,3 ( 211)-Dione A 3.24 2,3,6,7-tetrahydrospiro [bito-and-[3,2_g]nonene_5,3,,哚]_ Τ(1Ή)-ketone A 3.25 (3S)- 6-decyloxy-5-mercaptospiro[1·benzofuran_3 3,,丨哚]-2·(1Ή)-ketone A 3.26 (3R)-6-methoxy-5-fluorenyl snail Benzobenzofuran _3,3·_ρ5| 哚]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1063 - 201020257

Example No. Compound name CYP3A4 % inhibition 3.28 2',3',5,6-tetrahydrospiro[benzo[l,2-b ··5,4-b']dipyran-3,8'-[ 1,4]dioxolysene[2,3-old | 哚]-7'(6Ή)-ketooxime 3.29 6-decyloxy-2'-keto-oxime, 2'-dihydrospiro | >benzofuran-3,3Μ丨哚]-5-indolecarbonitrile A 3.30 6-fluoro-2'-keto-oxime, 2'-dihydrospiro[1-benzofuran_3,3·- W嗓]-5-carbonitrile A 3.32 4'-bromo-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3 '-啕哚]-2'(1Ή)-ketone A 3.33 4'-Fluoro-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxan Rare -8,3'-^丨哚]-2'(1Ή)-ketone A 3.34 4·-quinolin-3-yl-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene-8,3·-吲哚]-2'(1Ή)-ketooxime 3.35 4'-(4-phenoxyphenyl)-2,3-dihydrospiro [Bite and [2,3-g] [1,4] benzodioxanthene _8,3·-蚓哚]-2·(1Ή)-ketooxime 3.40 snail 5丨哚-3, 3'-thieno[2,3-f][l]benzofuran]_ 2(1H)-one 5,5·-dioxide A 3.41 snail [biting and [3,2-e][2 ,l,3]stupid and oxadiazole-8,3,-吲哚]-2Χ1Ή)-ketone A 3.42 6-Chloro-2,3-dihydrospiro[吱吱[ 3,2-f][i,4]benzodioxanthene-9,3·-4 astringent]-2,(1Ή)-ketone A 3.44 5,6-difluorospiro[1-benzo Furan_3,3,_啕哚]_2,(1,in-ketone B 3.45 5',6',7',8'-tetrahydrospiro[吲哚3,3,_荇[2,3 -b]furan]-2(1H)-ketoB 3.46 6-(2-methoxyethoxy)spirobenzofuran_3,3·,丨哚]-2'(1Ή)-ketone A 3.47 5-(2-methoxyethoxy)spiro-_benzofuran_3,3,_ρ?丨哚]-2'(ΓΗ)-ketone A 3.48 2,3-dihydrospiro[啥喃和[ 2,3-f][l,4]benzodioxanthene-7,3·-啕哚]-2,(1Ή)-ketone A 143924-sp-20091127-6 • 1064· 201020257 The name % CYP3A4 inhibits 3.49 2'3-dihydrospiro [吱π南和[2,3-g][i,4]benzodioxanthene-8,8'-[1,3> And [5,4-e]吲哚]_7,(6Ή)-ketooxime 3.50 4,6,,,methoxy-2,3_dihydrospiro[吱^[2,3-g][l , 4] Benzo-dioxene terpene-8,3,-吲哚]_2, (1, HV ketone A 3.51 snail [唉,[2,3-g] sucralin _8,3,-啕哚]-2,(1Ή)-net A 4 1 -(tetrahydrogen-2Η-jung-2-ylmethyl)_5,6-dihydrospiro[benzo[l,2-b: 5,4 -b']difuran_3,3,-ι·5丨哚]-2'(1Ή)-ketone A 4.2 1 -[(2-Alkyl-1-methyl-1Η-imidol-5-yl)methyl]_5,6_ a snail [benzo[l,2 -b : 5,4-b']二吱鸣-3 3,-ρ弓1 哚]-2'(1Ή)-ketone' Β 4.3 l'-[(2R)-E9 hydrogen furan-2-yl Methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2'(lΉ)-ketone A 4.4 l '-(3-Methylbutyl)-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]difuran-3,3'-啕哚]-2' ( 1Ή)-ketooxime 4.5 l'-tC'S:)-tetrahydrofuran-2·ylmethyl]_5,6-dihydrospiro[benzo[l,2-b:5,4-7]difuran-3,3 ,-W 哚]-Τ(1Ή)-ketone A 4.6 Γ-(tetrahydro-2Η- shout-4-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b: 5 ,4-b']difuran-3,3'-indole]-2'(1Ή)-keto A 4.7 5-[(2·-keto-5,6-dihydrospiro[benzo[i, 2-b: 5,4-b']difuran-3,吲哚]-1'(2Ή)-yl)indolyl]furan-2-carboxylic acid methyl ester 4.8 4.8 Γ-(1,4-dioxo圜-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2·(1Ή )-ketone A 4.9 Γ-{[1-methyl-3-(trimethyl)-!Η-ρ than 嗤-4-yl]fluorenyl}-5,6-dihydrospiro[benzo[i] ,2-b : 5,4-b]difuran-3,3'-吲哚] -2,(1Ή)-ketone Β 143924-sp-20091127-6 -1065 - 201020257

Example No. Compound name % inhibition of CYP3A4 4.10 Γ-(^Herhydro-2H-isanylmethyl)_5,6-dihydrospiro[benzo[l,2-b:5,47']difuran_ 3,3,_ρ5丨哚;ι_2'(ΓΗ)-63⁄4 A 4.11 2-[(2'-keto-5,6-dihydrospiro[stupid and like seven:5 4-7|]difuran-3, 3', 哚Η, (2Ή)-yl) fluorenyl]_; ι, 3-carbazole-4-reoxylate A A 4.12 l'n octyl)-5,6-dihydrospiro [benzo[ Take 7:5,4_b'] bis-p-am-3,3·-蚓哚>2, (1, HV ketone A 4.13 l'-(4-fluorobenzyl)-5,6-dihydrospiro [ Benzo[ub:5,4-b,] Dipyran-3,3'-啕哚]-2'(1Ή)-keto B 4.14 1'-Benzyl-5,6-dihydrospiro[Benzene [12_b : 5 4_b,]difuran-3,3'-啕哚]-2'(1Ή)-keto B 4.15 Γ-(biphenyl-4-ylindenyl)-5,6-dihydrospiro[benzene And [1,2 7: 5,4-b']dipyran-3,3'-啕嗓]·2,(γη)-_ A 4.16 4.17 1'-(tetrahydrofuran-3-ylindenyl)- 5,6-dihydrospiro[benzo[l,2-b. 5,4-b']diindole _3,3'-ρ5丨嗓]_2'(1Ή)-keto A bromoisoindole Zyrid-5-yl)indenyl]_5,6-dihydrospiro[benzo[l,2-b:5,47']difuran_3,3,-啕哚]_ 2,(1Ή)- Ketone B 4.18 14(5-bromofuran-2-yl Methyl]-5,6-dihydrospiro[benzo[l,2-b. 5,4-b']dioxin-3,3'-<»5 卜]-2,(1Ή) -嗣B 4.20 1'-(glycidyl-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']didentate"South-3 ,3'-bow|嗓]_2'(rHV ketone A 4.21 1 -[(1-ethyl-1Η-imidazol-5-yl)methyl]_5,6-dihydrospiro[benzo[l,2- b : 5,4-b']difuran_3,3,_吲哚]_, 2,(1Ή)-keto B 4.22 3-[(2'-keto-5,6-dihydrospiro[benzene And [i,2-b: 5 4-b,]-咕 丨哚 丨哚]-Γ(2Ή)-yl)f-based] benzene^-one XB 4.23 4-((2'-keto-5,6 -Dihydro-2H-spiro[benzene^-[6,5-b]glycan-3,3·-dihydroanthracene]_1'-yl)methanone A~~---- -—L 143924-sp-20091127-6 -1066 -

201020257

Example No. Compound name CYP3A4 % inhibition 4.24 4-[(2', yl-5,6-dihydrospiro[benzo[1,2-1):5,4-7,] diterpene-3,3'-吲哚]-Γ(2Ή)-yl)methyl]biphenyl_2_carbonitrile A 4.25 1 [(yloxy)methoxy]propyl}-5,6-dihydrospiro[benzo[l ,2-b : 5,4-b']difuran-3,3'-吲哚]-2'(ΓΗ)-_ B 4.26 1 -(2,3-dihydro-ι,4-benzoic Oxadecene _6_ylmethyl)_ 5,6-a snail [benzo[l,2-b : 5,4-b'] dioxin-3,3'-吲哚]-2 '(1Ή)-_ ' A 4.27 Γ-(2'|,3: benzoxadiazole_5_ylmethyl)_5,6-dihydrospiro[benzo[l,2-b: 5,4 -b,]difuran-3,3,-吲哚]-2'(1Ή)-keto B 4.28 l'-(2,^3-benzothiadiazole-5-ylindenyl)-5,6 -Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲哚]-2'(ΓΗ)-one B 4.29 l'-[(4-y Pegfosin-2-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dipyran-3,3,-吲嗓]- 2,(1Ή)-keto B 4.33 4'-Chloro-indole-{[5-(trifluoromethyl)pyran-2-yl]methylΙα-dihydrospiro[benzo[l,2-b : 5,4-b']difuran-3,3,-吲哚]-2'(1Ή)-keto B 4.34 4'-!^yl-14(2R)-izg Hydrofuran-2-yl Methyl]-5,6-dihydrospiro[benzo[1,2-b : 5,4-b']difuran-3,3'-throindole]-2'(1Ή)-one A 4.35 4 ·-Bromo-r-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3, 3,-吲哚]-2'(1Ή)-keto B 4.36 l'-(3-mercaptobutyl)-2,3-dihydrospiro[吱,[2,3-g] [1,4 Benzodioxanthene _8,3··峋哚]-2'(1Ή)-ketone A 4.37 1·-(tetrahydro-2Η-喊 喃 基 methyl)-2,3-dihydro Spiro[> Furan[2,3^][1,4]benzodioxanthene-8,3,-峋哚]-2'(1Ή)-ketone A 143924-sp-20091127-6 -1067- 201020257

Example No. Compound name CYP3A4 % inhibition 4.38 1'-(tetrahydro-2H-bran-2-ylmethyl)_2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene _8,3, mono-]-2'(1Ή)-ketone A 4.40 14(5-alkyl-1-methyl-1Η-amisole-2-yl)methyl] _2,3_Dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8,3'-啕哚]-2'(1Ή)-one hydrochloride B 4.41 Γ, (pyridin-2-ylmethyl)-2,3-dihydrospiro[furo[2,3-g] [1,4]benzodioxanthene]-2,( 1Ή)-ketone A 4.42 Γ-(acridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g] [1,4]benzodioxanthene _ 8,3'-吲哚]-2,(1Ή)-ketohydrochloride A 4.43 1'-[(25)-Tetrahydrofuran-2-ylindenyl]-2,3-dihydrospiro[吱喃[2,3-g][l,4]benzodioxanthene_8,3,_ρ5丨哚]-2'(1Ή)-ketone A 4.44 l'-[(2R),hydrofuran -2-ylindenyl]_2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3,_巧丨哚]-2Χ1Ή) -ketone A 4.45 1 -(1,4-I.lactino-2-ylmethyl)-2,3-diaza snail [biting u nan [2,3-g][l,4] benzo Dioxetene _8,3,_啕哚]-2Χ1Ή)-ketone A 4.46 Γ-(3,4-dioxin Benzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3'-called 哚]-2'(1Ή) -keto B 4.47 1'-(3,5-Dimethoxybenzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene _8,3'-啕哚]-2'(1Ή)·ketone B 4.48 Γ-(2,3-dihydro-1,4-benzodioxanthene-6-ylmethyl)-2, 3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-2'(1Ή)-ketone A 4.49 (R) -l'-{[5-(Tri 1 fluorenyl) 吱 °N-2-yl]methyl}-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzene And dioxanedecene-8,3'-啕哚]-2Χ1Ή)-ketone B 143924-sp-20091127-6 -1068- 201020257

Example No. — - - % inhibition of compound name CYP3A4 4.50 (3) Trifluoromethyl) oxime_2_yl] methyl b 2,3-dihydrospiro [吱,[2,3-g][l,4 Benzodioxanthene-8,3'-吲哚]-2'(ΓΗ)-ketooxime 4.51 (3)-called pyridin-2-ylmethyl)_2,3_dihydrospiro [2,3-g][l,4]benzodioxanthene_8,吲哚]_ 2'(1Ή)-ketone A 4.52 Γ-0 ratio bit-2-ylmethyl)_6,7 - Dihydrospiro [benzo-like seven: 4,5-7] difuran-3,3'-吲哚]·2'(1Ή)-ketone A 4.53 1'-[(2 magic-tetrahydrofuran_2_yl Methyl]_6,7_dihydro_511_spiro [bito-and-[3,2-g]decene-3,3·-吲哚]-2,(1Ή)-ketone A 4.54 Γ-{[5 -(trifluoromethyl)pyran-2-yl]methyl}·3,4-dihydro-2Η-spiro[c-buto[2,3-7][1,5]benzodioxanthene Alkene-9,3·-吲哚]-2,(1Ή)-ketooxime 4.55 Γ-0-pyridin-2-ylmethyl)-3,4-dihydro-2Η-spiro[吱,[2, 3-h][l,5]benzodioxanthylene sulphate -9,3'-< 哚]-2,(1Ή)-ketone A 4.56 2-methyl-indole-(3-methylbutyl Snail)[吱,[2,3-η[ι,3] benzopyrazole-7,3W丨哚]-2'(1Ή)-ketooxime 4.57 2-methyl-indole-(tetrahydro- 2Η-piperidin-4-ylmethyl) snail [biting murmur [2,3- illusion [1, 3] benzoheptazole-7,3'-啕哚]-2'(1'11)-ketooxime 4.58 2-methyl-1'-[(2 ft)-tetrahydrofuran-2-ylindole Base] snail [cough and [2,3-f][l,3]benzoan saliva-7,3'-p?b]2'(1Ή)- Ming A 4.59 1-methyl-l '-[(2R)-Tetrahydrofuran-2-ylindenyl]-1Η-spiro [furo[3,2-g][l,4]benzoindole-8,3'-吲哚]-2, 2,(1Ή,3Η)-dione A 4.60 1-methyl-l'-[(2R)-E9hydropyran-2-ylindenyl]spiro[ρofran[3,2-f][ l,3]benzoxazole-7,吲哚]-2,2'(1Η,1Ή)-dione A 4.61 6-methoxy-5-methyl-r-[(2R)-rahydrofuran -2-ylmethyl]spiro[1-benzofuran-3,3'-(4)哚]-2'(1Ή)-_ A 4.62 6-decyloxy-5-methyl-1'indoleidine- 2-ylmethyl)spiro[1-benzofuran-3,3'-indole]-2'(1Ή)-one B 143924-sp-20091127-6 -1069- 201020257

Example No. Compound name CYP3A4 % inhibits 4.63 6-methoxy-5-methyl-1,-(tetrahydro-2Η-»phen-2-ylmethyl)spiro[1-benzofuran-3,3, - 哚 哚]-2,(1Ή)-ketooxime 4.64 5-Fluoro-6-fluorenyloxy 4,-(tetrahydro-2 fluorene-pyran-2-ylmethyl)spiro[1-benzofuran- 3,3,-W哚]-2,(1Ή)-ketone A 4.65 5-Fluoro-6-methoxy group·ι,_(pyridine_2_ylindenyl)spiro[1-benzofuran-3 ,3'-吲哚]-2·(ΓΗ)-ketone A 4.66 5-fluoro-6-methoxy-i'-[(2R)-tetrahydrofuran-2-ylindenyl]spiro[1-benzo Furan-3,3,-啕哚]-2,(1'11)-鲷A 4.67 1'-fly-5-fluoro-6-methoxyspiro[1-benzofuran_3,3, -吲哚]-2·(1Ή)-net A 4.68 6-methoxy-14(2R)-tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran-3,3'-thirsty]- Γ(1Ή> ketone A 4.70 Γ-{[5-(trifluoromethyl)pyran-2-yl]methyl b 2,3,6,7·tetrahydrospiro[吱,[3,2-g Terpene-5,3'-吲哚]-2Χ1Ή)-keto B 4.72 l'-{[(2S)-5-ketotetrahydropyrrol-2-yl]indolyl} snail [ 口夫喃和[ 2,3-f][l,3]benzodioxanthene-7,3,-吲哚]-2\ΓΗ)-keto B 4.73 (2'-oxo snail [吱,[2,3 -f][l,3]benzodiazepine -7,3'-吲哚]-1'(2Ή)-yl)acetonitrile B 4.74 7'-(trifluoromethyl)-1,-{[5-(trifluoromethyl)-2-indolyl ]methyl} snail [吱,[2,3-f][l,3]benzodioxanthene-7,3'-嘀哚]-2'(1Ή)-net B 4.75 gas-based 2- 违 曱 曱 ] ] ] ] ] ] ] ] ] 咬 咬 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2哚]-2'(1Ή)-keto B 4.76 isopropyl-1,3-»» stopper. Sodium-5-yl)methyl]_7,-(trifluoromethyl)spiro[吱,[2,3-f][l,3]benzodioxene-7,3,-啕哚]-2,(1Ή)-keto B 4.77 1 -[(2-isopropyl-1,3-, oxazol-5-yl)methyl]spiro[吱,[2,3-f][l , 3] benzodioxene garden thin _7,3Ί ρ flower]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1070 - 201020257

Example No. Compound name CYP3A4 % inhibition 4.78 [1-cyclopropyl-3-(2f-oxaspiro[吱,[2,3-f][l,3]benzodioxolene-7,3 ·-吲哚]-Γ(2Ή)-yl)propyl]amino decanoic acid tert-butyl ester B 4.79 Γ-[4-(methylthio) aryl] snail [吱 并 阳 - 耶 苯And dioxin 圜 -7,3'-called 丨 noise]-2'(1Ή)-ketone B 4.80 3-(2'·oxaspiro[furo[2,3-f][i,3]benzene And dioxynene-7,3'-啕哚]-1·(2Ή)-yl)propanenitrile B 4.81 bromo-1,3-ρ-pyrazole-5-yl)methyl] snail And [2,3-f][l,3]benzodioxanthene _7,3'-»»5丨嗓]_ 2·(1Ή)-keto B 4.82 1·-{[2-amine 4-(trifluoromethyl)-indole, 3-oxetazole-5-yl]methyl} snail [bito-[2,3-f][l,3]benzodioxolene -7,3_-吲哚]-2'(1Ή)-keto B 4.83 6-Fluoro-5-methoxy-oxime-{[5-(tri-m-methyl)-brown-2-yl]methyl} Snail [1-benzopyrene-3,3'-p?budo]-2'(1Ή)-keto B 4.84 4'-gas-based-2'-oxo snail [ρ矢喃[2,3- f][l,3]benzodioxol-7,3,-old oxime)acetonitrile A 4.85 Γ-[(2-amino-1,3-thiazol-4-yl)indolyl] Snail [吱,[2,3-f][l,3]benzodioxolene-7, 3,_吲哚> 2'(1Ή)-keto B 4.86 4 -Bromo-1 -[(5-alkyl-2-p-tombryl)indolyl] snail [biting and argon [2,3- f][l,3]benzodioxanthene·7,3ι_ρ5丨哚]-2'(1Ή)-keto B 4.87 1 -[(5-carbyl-2-thienyl)methyl]_2, -_基_Γ,2,_ _A nitrogen snail [吱,[2,3-f][l,3]benzodioxan^_7,3'-β丨嗓]-7'·曱月青B 4.88 1 -[(2-isopropyl-1,3^- oxazol-4-yl)indolyl]-indole, 2·-dihydrospiro[吱,[2,3-f][i, 3] Stupid and 1 gas, urethane-7,3'-吲哚]-7,-曱carbonitrile ------... B

143924-sp-20091127-6 -1071 - 201020257 吲哚]-5-carbonitrile; Γ-(diphenylmethyl)-2'-keto-l',2'-dihydrospiro[μbenzofuran_ 3, κ哚]_6_carbonitrile; 1-(phenylindenyl)_5,6-difluorospiro[1-benzofuran_3,3,_la 哚]_2, (1Ή)-one; 1 - (monophenylmethyl)_6-(2-methoxyethoxy)spiro[μbenzofuran_3,3,_吲哚]·ΑΓΗ)-one; 5_(lower oxy)-Γ-(two Benzyl) snail [μbenzofuran_3,3,_吲哚]_2, (1Ή) ketone; 1 _(monophenylhydrazinohydroxyspirobenzofuran-3,3'-吲哚]-2, (1Ή)-ketone; ❿

1 · (Diphenylmethyl)-5-(2-methoxyethoxy) spiro [μbenzofuran_3,3,啕哚]_ 2,(1Ή)-one; -One methyl group) -2,3-dihydrospiro[吱,[2,3<][1,4]benzodioxanthene]-2,(1,Η)-one; r-(diphenylmethyl Snail [biting and [3,2_e][213]benzoxadiazole_8,3,10] _ 2'(1Ή)-one; 6 gas group 1 (-benzyl)_2,3_ Dihydrospiro[吱喃耶,4]benzodioxanthene-9Χ 哚]-2'(1Ή)-鲷; (benzyl)-9-carbyl_2,3_dihydro-snail Bufu. Nanhe [2,3柳,4]benzodioxanthene·8,3,,哚]-2'(1Ή)-one; benzyl) 7,8-hydrogen_6Η_喃[2 3_幻咣烯啕哚]_ 2'(1Η)-ketone; (benzyl) snail [唉π南和[2,3_g>奎噪音]_2,(10))嗣; 6-methoxy -2'-brewed base- & 丄田'-一风螺[1-Bist and furan-3,3··吲哚carbonitrile; Fluorite 2 keto-1 '2'-hydrospiro[ 1_benzofuran-3,3,-吲哚]-5-carbonitrile; 2'.yl-r,2'-dihydrospirobenzofuran_3, mercapto nitrile; 143924-sp- 20091127-1 201020257 Example No. Compound name CYP3A4 % inhibition 4.89 4·-Chloro-indole-[(5-carbyl-2-quinolyl)methyl] sulphide [吱,[2,3-f][ l,3] stupid and dioxynene _7,3·-吲哚]-2'(1Ή)-ketooxime 4.90 4匕chloro-poly{[5-(trifluoromethyl)-2-furan曱]曱基μ累[ρ失喃[2,3-f][l,3]benzodioxolene-7,3·-»5 丨哚]-2'(ΓΗ)-ketone oxime 4.91 4'-Chloro-indole-[(2-isopropyl-1,3-pyrazole-4-yl)methyl]spiro[吱,[2,3-f][l,3]benzo Dioxolene-7,3'-吲哚]-2·(ΓΗ)-ketooxime 4.92 4'-[6-(didecylamine aridin-3-yl)-1,-{[2- (1-methyl B )-1,3-oxazol-4-yl]fluorenyl} snail [吱,[2,3-f] [1,3]benzodioxene _7,3,-p?丨哚]-2,(1Ή)-_ Β 4.93 3'-[2-(Fluoromethyl) yl]_2,3-dihydrospiro [bite and [2,3-g][l,4]benzene Dioxo-enolene _8, Γ^ ]_ 2'(3Ή)-ketooxime 4.94 3-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g]] [l,4]benzodioxanthene-8,3'-峋哚]-1,(2Ή)-yl)indenyl]benzonitrile-5.95 Γ-(Winter, gas-based-3-methoxy Base, _2,3_dihydrospiro 1; oxime[2,3-g][l,4]benzodioxanthene 哚]_ 2乂1'11)-ketooxime 4.96 4- LC" gas-2,3-dihydrospiro[furo[2,3-g][i,4]benzo-l-l-cluene-8,3'-...嗓]-Γ(2Ή)-yl) Methyl 1 benzonitrile Β 4.97 Γ-(4-iso, ol-5-ylindenyl)_2,3_dihydrospiro [biting and [2,3-g][l,4] stupid and dioxane圜 圜 _8,3,_ρ5丨哚2'(1Ή)-ketone JA 4.98 1 -{[6-(difluoroindolyl)-pyridinyl]methyl b 2 3_ one, [sniff, and [ 2,3-g][1,4]benzodioxanthene-lean-8,3·-吲哚]-2'(1Ή)-keto B 4.99 1 -(4-iso, 嗤-5-yl芊基)_3_methyl snail [味喃[3,2-f][l,2] benzopyrene 吟5,3.5 卜朵ι_ 2 '(1Ή)-ketone A 143924-sp-20091127-6

(S 201020257 Example No. Compound name CYP3A4 % inhibition 4.100 fluoro group * * 唆-2-yl) methyl]-2,3-dihydro snail [bite mer to [2,3-g] [l, 4] Benzodioxanthene _8,3'-thirsty]-2'(1Ή)-one

A 4.101 l'-[(3-Fluoro-peptidyl-2-yl)methyl]-2,3-dihydrospiro (V-ββ南和[2,3-g][l,4]Benzene Dioxoenene-8,3'-anthracene ketone

A 4.102 Γ-〇»比比特-2-基曱基)-4'-ι»奎林-3-yl-2,3-dihydrospiro[furo[2,3-g][l,4] Benzodioxanthene _8,3·- 哚 哚]-2'(1Ή)-ketone

B 4.103 4'-(4-Phenoxyphenyl)-1'-(acridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene _8,3'·啕哚]-2'(1Ή)-one

A 4.104 1·-[(3,5-Difluoropyridin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodiox Terpene-8,3'-p?丨哚]-2'(1Ή)-ketone

A 4.105 2·-keto-indole-(pyridin-2-ylindenyl)-1',2·-dihydrospiro[1-benzofuran-3,3·-吲哚]-6-carbonitrile

A 4.106 3-{[(8S)-2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8,3 '-吲哚]-Γ(2Ή)-yl]methyl}benzonitrile

A 4.107 (8S)-r-[(5-fluoropyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodiox Luyuan _8,3· 吲哚]-2'(1Ή)-ketone

A 4.108 (8S)-l'-[(3-Fluoropyridin-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzo Dioxetene _8,3'-吲哚]-2'(1Ή)-one

A 4.109 (S)-r-(2-ketobutyl)-3,7-dihydro-2-indole-spiro[benzofuro[5,6-b][l,4]dioxolene- 8,3,-Dihydro(4) 哚]-2'-one

A 143924-sp-20091127-6 -1073 - 201020257 Example No. Compound name % inhibition of CYP3A4 ----- ------ ABA 4.110 14(4-Fluoropyridin-2-yl)methyl] -2,3-dihydrospiro[2,3-g][l,4]benzodioxolene _8,3,_吲哚]-2'(1Ή)-ketone 4.11 Γ-(2 , 3-dihydro-1,4-benzodioxanthene 2·-keto-oxime, 2'-dihydrospiro[1_benzofuran_3,3,_吲哚]-6 -carbonitrile 4.112 14(3-carbenylpyridin-2-yl)methyl]·2,3-dihydrospiro[flavor, Nanhe [2,3-g][l,4]benzodioxan Alkene_8 3,_吲哚WH)-ketone 4.113 1 -[2·(difluoroindolyl)+yl]-2,3-dihydrospiro [bite and [2'3-g][l,4 ] 本弁一氧陆圜稀»»朵ι_ 2,(1Ή)-ketone 4.14 (8R)-l'-[2-(trifluoromethyl)hanyl]_2,3_dihydrospiro[吱[2,3-g][l,4]benzodioxanthene _8,3'-p? Buduoι_ 2'(1Ή)-ketone A 4.116 (8S)-l'-[2-( Tris-1 methyl)-yl]_2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3,_吲哚ι_ 2' ( ΓΗ)-ketone A 4.118 Γ-(2,1,3-benzoxadiazole·5-ylmethyl)_2 3_dihydrospiro[furo[2,3-g][l,4]benzo Dioxetene _8 3, _ ^ 丨哚]-2·(ΓΗ)-ketone' B 4.119 1 -(1,3-Benzo-pept-2-ylmethyl)-2,3-dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene_8,3,_吲哚]_ 2,(1Ή)-keto B 4.120 methyl-1Η-benzimidazol-2-yl)methyl ]_2,3-Dihydrospiro[唉,[2,3-g][l,4]benzodioxene-8,3'-吲哚]-2Χ1Ή)-net B 4.121 1'- {[2-(1-methylethyl)-1,3-pyrazol-4-yl]methyl}_2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodioxanthene-W-吲哚]-2·(1Ή)-keto B 4.122 Γ-(2,1,3-benzoxadiazole·5-ylmethyl)_2,3_dihydrogen Snail [furo[2,3-g][l,4]benzodioxanene·8,3,-丨哚]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1074 -

(S) 201020257

Example No. Compound name CYP3A4 % inhibition 4.124 Γ-0 pyridine-2-yl fluorenyl) snail [吱,[3,2-e][2,l,3]benzoxadiazole-8X哚]- 2'(1Ή)-ketone A 4.125 Γ-0-pyridin-3-ylindenyl) snail [吱,[3,2-e][2,l,3]benzoan II" -8,3 ·-吲嗓]-2'(1Ή)-ketone A 4.126 6-Chloro-indole-〇»比定-2-ylmethyl)-2,3-dihydrospiro [bite-and-[3,2 -f][l,4]benzodioxanthene-9,3Μ丨嗓]-2,(1Ή)-keto B 4.129 1-[(2R)-tetrahydrofuran-2-ylmethyl]-5· ,6·,7·,8·-tetrahydrospiroindole 哚-3,3'-indolo[2,3-b]furan]-2(1Η)-_ A 4.130 1'-〇比 bit-2- Methyl) snail [ρ 喃 并 [2,3-g] P Kui»» n n-8,3,-吲哚]-2'(1Ή)-ketone A 5 Γ-[(2-A Oxypyrimidin-5-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dipine;3,31^丨嗓]-2 '(1Ή)-ketone A 5.1 7'-gas-indole-((5-(trifluoromethyl)pyran-2-yl)methyl)·5,6-dihydro-2Η-spiro[benzo ρ夫味和[6,5-b] 3 3,3*-二气〃5丨嗓]-2'-嗣B 5.2 (3R)-l'-(3-mercaptobutyl)-5, 6-Dihydrospiro[benzo[i,2-b : 5,4-b]difuran-3,3'-4丨哚]-2'(1Ή)-one B 5.3 (3R)-r-pentyl —5,6-dihydrospiro[benzo[l,2-b:5,4-7]difuran-3,3^ 哚]-2'(1Ή)-keto B 5.4 (3R)-r- (pyridine-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-啕哚]-2, (1Ή )-ketone A 5.5 (3R): l'-{[5-(trifluoromethyl)p-fluoroyl]methyl b 5,6-dihydrospiro[benzo[l,2-b: 5,4 -b']二吱鸣-3,3'-ι·5丨哚]-2·(1Ή)-keto B 5.6 (3S)-l'-indolepyridin-2-ylmethyl)-5,6 - dihydrospiro[benzo[l,2-b:5,4-b']dioxan-3,3^丨哚]-2,(1Ή)-ketone A 5.7 (33):1'-{ [5-(Trifluoromethyl)c-but-2-yl]methyl}_5 6_二乳螺[benzo[l,2-b:5,4-b,]dioxan-3,3, -ρ弓1 哚]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1075- 201020257 Example No. Compound name CYP3A4 % inhibition 5.8 3-mercapto-purine-{[5-(trifluoroanthracene) Alkyl-2-mercapto} snail [吱,[2,3-f][l,3]benzoxazole-7,3W| 哚]-2,2'(1Ή,3Η) -dione oxime 5.9 [-{[6-(Trifluoromethyl)>pyridin-2-yl]indolyl}-2,3-dihydrospiro-dea-[2,3-g][l, 4] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-ketooxime 5.10 14[2-(Trifluoromethyl)acridin-3-yl]methyl}-2 , 3-two Snail [吱,[2,3-g][l,4]benzodioxanthene-8,3,- 哚 哚]-2,(1Ή)-ketone A 5.11 Γ-{[3-( Trifluoromethyl)indol-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3 '-峋哚]-2'(1Ή)-ketone----- A 5.12 Γ-{[4-(Trifluoromethyl)acridin-3-yl]f-yl}-2,3-dihydrospiro [Bite and [2,3-g][l,4]benzodioxanthene-8,3'-(5)哚]-2'(1Ή)-ketone--~~-_ B 5.13 1 _ [(6-Chloro-purine-2-yl)methyl]-2,3-diazaspiro[pf-pyrano[2,3-g][l,4]benzodioxanthene-8 ,3,-吲哚]-2'(ΓΗ)-ketone ________ B 5.14 Γ-[(2-methoxypyrimidin-5-yl)methyl]-2,3-dihydrorano[2, 3-g][l,4]benzodioxanthene_8,3,-^丨哚]-2ΧΓΗ)-ketone-------SA 5.15 1 -[(6-methyllactyl p Bis-3-yl)methyl]-2,3-dihydrospiro[p-f-[2,3-g][l,4]benzodioxolene_8,3,_^丨哚]-2'(1Ή)-ketone^----_ A 5.16 (8S)-1'7-to-till-2-ylmethyl)-2,3-dihydrospiro [bite [2,3-g] ][l,4]benzodioxanthene _8,3,_ρ5丨哚]-2'(1Ή)-ketone A 5.17 (8S)-l'-[(2-曱 嘴 mouth bite-5 -基)曱基] 螺[吱喃和[2,3 -g][l,4]benzodioxol-8,3'-吲哚]-2'(1 gen)-ketone A 5.18 (8S)-r-(pyrimidin-2-ylmethyl) -2,3_Dihydrospiro[2,3-g][l,4]benzodioxanthene_8,3,_„引哚]-2'(1Ή)-ketone' A --- 143924-SP-20091127-6 -1076 - 201020257

Example No. Compound name % inhibition of CYP3A4 5.19 6-Methyl-indole-(pyridin-2-ylindenyl)-2,3-dihydrospiro[1,4-dioxopinene [2,3-fH哚-8,3'-啕哚]-2,,7(1Ή,6Η)-dione A 5.20 4'-Fluoro-indenyl-{[3-(trifluoromethylacridin-2-yl)- Keb 2,3-di-spiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-呻哚]-2'(1)-ketone A 5.21 Γ-[(2,2-Difluorocyclopropyl)methyl]-2,3_dihydrospiro[> Furano[2,3-g][l,4]benzodioxan Alkenylene-8,3'-吲哚]-2'(ΓΗ)-ketone A 5.22 Γ-methyl-2,3-dihydrospiro[Ethylene[2,3-g][l,4]benzene And dioxerem-8,3'-吲哚]-2'(1Ή)-ketone A 5.23 Γ-{[4-(trifluoromethyl)-1,3-oxazol-2-yl]anthracene }}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-2·(ΓΗ)-ketone B 5.25 9-Fluoro-indenyl-(pyridin-2-ylmethyl)-2,3-dihydro-spiro[M-benzo[2,3-g][l,4]benzodioxanthene -8,吲哚]-2'(1Ή)-keto B 5.26 9-Fluoro-indenyl-{[3-(trifluoromethylcyclopyridin-2-yl)indolyl 2,3-dihydrospiro[吱 并[2,3-g][l,4]benzodioxanthene-8,3·-啕哚]-2·(1Ή)-ketone A 5.27 9-fluoro-14 5-hydroxypyridin-2-yl)methyl]-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8,3'-吲酮]ketone B 5.28 Γ-(pyridin-2-ylmethyl)-7,8-dihydro-6Η-spiro-[furo[2,3-g]decene-3,3,-吲哚]- 2'(1Ή)-keto B 5.29 Γ-{[3-(trifluoromethylcyclopyridin-2-yl)indolyl 7,8-dihydro-6Η-spiro[吱.南和[2,3- g] butylene-3,3W broxo]-2\1Ή)-ketone A 5.31 Ηpyridine·2-ylindenyl) snail (tetra) 哚-3,3,-thieno[2,3-f] [1] Benzofuran]-2(1H)-one 5,5'-dioxide A 5.32 1'-(pyrimidin-2-ylmethyl)-2,3-dihydrospiro[c-c-[2,3- g] [1,4]benzodioxanthene-8,3·-吲哚]-2·(1Ή)-ketone A 143924-sp-20091127-6 • 1077 · 201020257

Example No. Compound name CYP3A4 % inhibition 5.33 Γ-[(4,6-Dimethoxypyrimidin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene-8,3,-吲哚]-2,(1Ή)-ketooxime 5.34 6-(2-carboxyethyl ethoxypurine'-(acridin-2- Methyl) snail [1-benzofuran-3,3.?丨哚]-2'(1Ή)-ketone A 5.35 5_(2_methoxyethoxy Η'-Ο1-pyridin-2-yl Methyl) snail [ι_ benzofuran-3,3Μ丨哚]-2'(1Ή)-ketone A 5.36 Γ-^ than biti-2-ylmethyl)-2,3-dihydrospiro|>喃[1,4]benzodioxanthene_7,3L啕哚]_2,(ΓΗ)__ A 5.37 Γ-{[3-(trifluoromethyl)pyridin-2-yl]A }}-2,3-dihydrospiro[吱,[2,3<][1,4]benzodioxanthene-7,3'-吲哚]-2'(1Ή)-net A 5.38 6-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxol-7,3·-吲哚]4·(2Ή)-yl)曱基] pyridine-2,4(1Η,3Η)-dione A 6 [-[(5-alkyl-1,2,4-oxadoxazol-3-yl)methyl] snail [scream And [2,3-f][l,3]benzodioxene _7,3,-吲哚]-2\1Ή)-keto B 6.1 4-alkyl-indole-[(5-chloro Base-1,2,4-ν»塞二》坐_3-基)methyl] snail [ Pyrano [2,3-f] [l, 3] -7,3-benzodioxol-ene Wu Park.哚]]-2·(1Ή)-ketone B 6.2 ___ — —__ 5,6-monomethyl-hydrazine-(tetrahydro-2Η-'pai-2-ylmethyl) snail [ι_benzofuran- 3,3'-啕哚]-2'(1Ή)-纲' B 6.3 Γ-[(3-Chloropyrimidin-2-yl)indolyl] snail [吱 并[2 3^ [1,3 Benzodioxanthene -7,3^5 noisy]_2,(1,Η)-keto B 6.4 Γ-{ [3-(2,6-diphenyl)-5-fluorenyl ,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, 11)-keto B 6.5 Γ-({2-[4-(trimethylmethyl)phenyl]-l,3-p sev- _4-yl} fluorenyl) snail [sniffing [2,3- f][l,3]benzodioxanthene-7,3,-啕哚]-2,(1Ή)-ketone B 143924-sp-20091127-6 • 1078 - 201020257

Example No. Compound name CYP3A4 % inhibition 6.6 l'-[(5-phenyl-1,3,4-oxadiazol-2-yl)indolyl] snail [吱,[2,3-ί][1 ,3]benzodioxanthene-7,3'-啕哚]-2'(1Ή)-ketooxime 6.7 l'-{[5-(4-phenylphenyl)-1,3,4- Oxazol-2-yl]methyl} snail [吱,[2,3-f][l,3]benzodioxolene _7,3,_ 吲哚]-2'(1Ή) -ketooxime 6.8 1'-([1,3]carbazolo[4,5-bruppyridin-2-ylmethyl) snail [吱,[2,3-f][l,3]benzo Dioxolene·7,3·-啕哚]-2ΧΓΗ)-ketone A 7.1 1'-[3-(Trifluoromethyl)-yl]-2,3-dihydrospiro [bite-and-[2] ,3^][1,4]benzodioxanthene-8,3'-吲哚]- 2\1Ή)-ketone A 7.2 5-[(2'-keto-2,3-dihydrol Snail [吱,[2,3-g][i,4]benzodioxanthene-8,3'-啕哚]-Γ(2Ή)-yl)methyl]furan-2-carboxylic acid Methyl ester Β 7.4 (R)-r-pentyl-2,3-dihydrospirofurfuryl οg][i,4]benzodioxanthene-8,3'-<哚]-2 '(1Ή)-ketooxime 7.5 1'-Hexyl-2,3-dihydrospiro[Ρ,[2,3_g][1,4]benzodioxanthene-8,3'-啕哚]-2·(1Ή)-ketooxime 7.6 1'-(2_cyclo-1,ethyl)-2,3-dihydrospiro[吱,[2,3-g] [1,3]benzo Oxygen lanthanum _8,3'-吲嗓]_2, (1Ή> ketone A 7.7 Γ_(2_ethyl^ _ethyl)-2,3-dihydrospiro [味喃[2 3_g;j [1 , 3] benzodioxanthene 嫦 _8,3··吲嗓]_2, (i'h)_class A 7.8 1'-(4_甲赘今丁夸氢螺[唉,[2,3_g] [1,3] benzodioxanthene _8,3'-吲嗓]_2, (1,11)-keto A 7.9 1'-〇曱^ propyl;)-2,3_dihydrogen Snail [吱3[g][[], [3, 3] benzodioxanthene-8,3'-吲u ι_2·(ι,η)-ketone A 7.10 1'-(3-Nanjin ))-2,3-dihydrospiro[吱,[2,3_幻[1,3]benzodioxanthene_8,3,_吲NO]_2·(ι,η)-ketone A 143924-sp-20091127-6 -1079- 201020257

Example No. Compound name CYP3A4 % inhibition 7.11 Γ-(1,3-ρ-propazol-5-ylmethyl)-2,3-dihydrospiro [c-buto[2,3-g][l,3] Benzodioxanthene _8,3'-峋哚]_ 2'(ΓΗ)-keto B 7,12 1 -{[5-(dimethyl fluorenyl) ρ than dimethyl group 2, 3-dihydrospiro[,,[2,3-g][l,3]benzodioxanene-8,蚓哚]-2'(rH)-_ B 7.13 1'-{[3 -(trifluoromethyl)acridine·2_yl]indolyl 2,3_dihydrospiro[唉,[2,3-g][l,3]benzodioxene _8, 3,-蚓哚]-2,(1Ή> Ketone B 7.14 Γ-[(3-Acridine-3-ylisoxazole-5-yl)methyl]_2,3_dihydrospiro 2,3-g][l,3]benzodioxanthene-8,3'-W 嗓]-2,(1Ή)-鲷B 7.15 (8R)-l'-{[3-(three Fluoromethyl) 峨_2_基]曱基卜 2,3 Dihydrospiro[,,[,,,,,,,,,,,,,,,,,,,,,,,,,,,,, -2Χ1Ή)-纲A 7.16 Ν,Ν-二f基_3_[(2'keto-2,3_dihydrospiro[bit, benzo[2,3-g][l,4]benzodioxole圜 圜 _8 3, _ 吲嗓] _ 1 '-(2 Ή)-yl) methyl] benzene hydrazide B 7.17 1 -[3-(moffene-4-yl) fluorenyl] _2,3_Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3 _ 啕哚]-2'(1Ή)-keto B 7.18 1 -[(4-methyl-1,2,5-oral diazol-3-yl)indenyl]_2,3_dihydrospiro And [2,3-g][l,4]benzodioxanthene_8,3'-啕哚]-2Χ1Ή)-ketone A 7.19 1 -(2,3-difluorobenzyl)·2 , 3 · Dihydrospiropyrene [2 3 g] [1,4] Ben-Oxygen Park Rare-8,3'-p5 Noisy 1-2·(1'Η)-ketone B 7.20 1 Gas-based dihydro snail [biting and argon [2,3-g] [1,4] dioxin oxalate _8,3'_ noisy]_2, (rH) ketone B 7.21 1 _(4 two Fluoro)-2'3_dihydrospich-[2,3-g][l,4] Benzodioxene-8,3'-p?b]_2,(i, h)-_ B 143924-sp-20091127-6 -1080 - 201020257

Example No. Compound name CYP3A4 % inhibition 7.22 Γ-(2-Alkyl-4-fluorobenzyl>2,3_dihydrospiro[吱,[2,3-g][l'4]benzoic Oxygen decene _8 3, 丨哚2·(1Ή)-ketone JA 7.23 Γ-[(1-methyl-1H-benzotriazol-5-yl)methyl]_2 3_dihydrospiro [bite M-[2,3-g][l,4]benzodioxanthene-8,3·-啕哚]-2,(1,H)-keto A 7.24 1 -[(3-difluoro曱oxy)]]]]3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8 3ι_吲哚2'(1Ή)-ketone JB 7.25 Γ-[(2-Fluoro-6-trifluoromethyl)-yl]_2,3-dichlorospiro[Blowing-Nan[2,3-g][l,4]benzodioxanthine Alkene_8,3,_ρ5丨哚]-2'(ΓΗ)-ketone A 7.26 l'-[(2-Fluoro-5-trifluoromethyl)-yl]2,3_dihydrospiro[bite啥 and C2,3-g][l,4]benzodioxanthene_8,3,_吲哚]-2'(ΓΗ)-ketone A 7.27 7.28 Γ-[(2-trifluoromethoxy) Benzyl]_2,3_dihydrospiro[,[2'3-g][l,4]benzodioxolene-8,3,_吲哚2'(1Ή)-one A Γ-[2-(2,2,5-trimethyl_ι,3_dioxoland winter)ethyl]_ 2,3-dihydrospiro [biting mers [2,3_§][1, 4] benzodioxanthene-8,3,-吲哚]-2, (1 )-keto B 8 r-[(2S)-l,4-dioxolybdenyl-2-ylmethyl]spiro[吱,[2,3-f][l,3]benzodioxanthene Alkene_7,3,_啕哚]_ 2,(1Ή)-keto B 8.1 7'-gas-l'-[(2R)-tetrahydrofuran_2-ylindenyl]_5,6-dihydrospiro[ Benzo[l,2-b:5,4-b,]difuran-3,3'-吲哚]-2'(1Ή)-ketone A 8.2 7'-Fluoro-r-[(2R)- Tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲哚]-2'(1Ή) -ketone A 8.3 4-fluoro-7--fluorenyl-l,-[(2R)-tetrahydrofuran-2-ylmethyl 5,6-dihydrospiro[benzo[[7:5,4-7]] Difuran-3,3,-吲哚>2·(1Ή)-ketone' B ------ 143924-sp-20091127-6 -1081 - 201020257 2.3- Dihydrospiro [bite and [3, 2-f][l,4]benzodioxanthene_9,3,_啕哚]-2'(1Ή)-one; 5,6-difluorospiro[1-benzofuran_3, 3'-吲哚]-2'(1Ή)-one; 6-(2-methoxyethoxy) snail [ι_笨和furan_3,3,_ρ5丨哚]_2,(ι,η) 5-ketone; 5-(2-decyloxyethoxy) snail [1· benzofuran _3,3,_吲哚]_2, (1Ή)-ketone; 2.3-dihydrospiro [biting and argon [2] , 3-f][l,4]benzodioxanthene_7,3,_吲哚]_2, (ι'η) ketone; [吱D南和[2,3-g]峻崎淋-8,3'-4嗓]-2,(1Ή)-ketone; 2·-keto-l'-〇比 bit-2-yl曱Base)_1',2,_dihydrospiro[]L_benzofuran_3,3,·(f)哚]_6_phthalonitrile; 1 -(2,3-dihydro-1,4-benzodioxan Benzene_6_ylmethyl)_2,__yl-Γ,2,dihydrospiro[1-benzo-aramid-3,3'-θ丨嗓]-6-indoleonitrile; 2-ylmethyl) snail [吱,[3,2_印2,13]benzoh-diazole _8,3,吲哚]-Τ(ΓΗ)-one; Γ-(pyridine-3- Methyl) snail [吱,[3,2<][2,13]benzoxadiazole_8,3,_吲哚]-2'(1Ή)-one; 4- [(5,6 -difluoro-2'-oxaspiro[1-benzofuran_3,3,fluorene,(2Ή)yl)indenyl]hexahydro11-pyridin-1-one acid tert-butyl ester; 6- (2-methoxyethoxy)-1,-(pyridine-2-ylmethyl)spiro[]L benzofuran-3,3,...丨哚]-2'(1Ή)-one; 5- (2-decyloxyethoxy group> 1'-(pyridin-2-ylindenyl)spiro tl_benzofuran_3 3, _ 丨哚 丨哚]-2'(1Ή)-one; Than-2-mercapto)-2,3-monohydrospiro[唉,[2,3_·,4]benzodioxene-7,3'-W 哚]-2' (1Ή )-ketone; 143924-sp-20091127-l -no. 201020257

Example No. Compound name CYP3A4 % inhibition 8.4 Γ-pentane&yl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3 ·-啕哚]-2'(1Ή)-keto B 8.5 (8R)-l'-[(2R)-l,4-dioxolyl-2-ylmethyl]_2,3_dihydrospiro [吱 并[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-阙A 8.6 (8R)-r-[(2S )-l,4-dioxoindolin-2-ylindenyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 ,3'-啕哚]-2·(1Ή)-ketone A 8.8 (8S)-r-[(2R)-l,4-dioxaindole-2-ylindenyl]_2,3_dihydrospiro [吱吱[2,3-g][l,4]benzodioxanthene]>2'(1Ή)-ketone A 8.9 1'-[(2 ft)-tetrahydrofuran_2_ Methyl]_6,7-dihydrospiro[benzo[1,2-7:4,5-b']difuran-3,3,-吲哚]-2'(1Ή)-ketone A 8.10 1' -[(2,1,4-dioxaindole-2-ylindenyl]_6,7-dihydrospiro[benzo[l,2-b:4,5-b']di-n-but-3 ,3^弓丨哚]-2Χ1Ή)-ketone A 8.11 l'-[(2R)-tetrahydrofuran_2_ylmethyl]_3,4-dihydro-2H-spiro [weiran[2,3-h ][l,5]benzodioxyl octadecene-9,3'-吲哚]-2'(ΓΗ)-ketone A 8.12 l'-[(2R)-l,4-dioxane -2-ylindenyl]-3,4-dihydro-2-indole-spiro[pf-pyrano[2,3-h][l,5]benzodiazepine-decenene-9,3'-W哚]-2·(1Ή)-ketone A 8.13 l'-[(2S)-l,4-Dioxaindole-2-ylindenyl]-3,4-dihydro-2Η-spiro [2,3-h][l,5]benzodioxine heptadecene-9,3,-W 哚]-2,(1Ή)-_ A 8.14 3-mercapto-l'-((( R)-izg hydrogen furan-2-yl)methyl)_2Η-spiro[benzopyrene °Nan[6,5-d]p vomit-7,3'-dihydro^丨哚]-2,2 '(3H,6H)-dione A 8.15 7'-Fluoro-oxime-0-pyridin-2-ylindenyl)-3,7-dihydro-2H-spiro[benzofuran[5,6- b][l,4]dioxene _8,3'-dihydroanthracene-2'-one A 143924-sp-20091127-6 -1082 · 201020257 Example number Compound name CYP3A4 % inhibition 8.16 7 '-Fluoro-indole-((3-(tri-methyl)p) 2,7-dihydro-2Η-spiro[benzo,[5,6- b][l,4]dioxolene-8,3'-dihydroanthracene-2·-one A 8.17 3'-[2-(difluoromethyl)-yl]-2,3- Dihydrospiro[吱,[2,3-layer][1,4]benzodioxolene-8,1'-茚]-2'(3Ή)-ketone A 8.18 Γ-[(5- Fluoro-based ρ than -3-yl) fluorenyl]-2,3-dihydrospiro[吱π南和[2,3-g][l,4]benzodiox陆圜烯_8,3'_吲哚]-2'(1Ή)-keto B 8.19 (8S)-l'-[(5-fluoropyridin-3-yl)methyl]_2,3-dihydro Snail [吱,[2,3-g][l,4]benzodioxanthene_8,3,_啕哚]-2'(1Ή)-ketone A 9 3-methyl-1' -{[5-(Trifluoromethyl) succinyl-2-yl]methyl} snail [furo[3,2-f][l,2] benzisoxazole_5,3,_啕哚]-2'(1Ή)-keto B 9.1 Γ-[2:(2-decyloxyethoxy)ethyl]_5 6-dihydrospiro[benzo[l,2-b : 5,4-b ']difuran oxime]-2,(1Ή)-ketone B 9.2 l'-{|^2S)-5-ketotetrahydropyrrole_2-yl]fluorenyl}_5,6-dihydrospiro[benzene And [l,2-b : 5,4-b·]dipyran-3,3,-^| 哚]-2·(1Ή)-ketone A 9.3 1'-[2:(2-_ base- ΐ, 3-tetrahydro "ττω_3_yl)ethyl]_5,6·dihydrospiro[benzo[l,2-b: 5,4-b']difuran_3,3'_吲哚]- 2-(1Ή)-one ------ B 9.4 9.5 1 -(4-Acridine-2-ylindenyl)_5,6-dihydrospiro [benzophenidyl, 2:7: Μ- b']difuran-3,3'-(6)哚]-:r(rH)-one A 1 -(oxaridin-2-ylindenyl)-5,6,dihydrospiro[benzo[pb : 5 , 4-b'] biceps _3,3'-吲哚]_2'(1Ή)-class A 9.6 1 -('bitate-4-ylmethyl)-5,6-dihydrospiro [stupid Like seven: —5,] difuran-3,3· -啕哚]-2·(1Ή)-net A 9.7 1 -0, _ -2-ylmethyl)-5,6-dihydrospiro [benzoate, 2:7,5,4-b'] -3-3,3·-^丨哚]-2·(1'Η)-_ A 143924-sp-20091127-6 -1083 - 201020257 Example number % inhibition of compound name 9.8 Fluoro-1-benzofuran 2-yl)methyl]_5 6_dihydrospiro[benzo[l,2-b : 5,4-b']didentate _3 哚]-2'(1Ή)-ketone' Β 9.9 1' - (.荅-3-ylmethyl)-5,6-dihydrospiro[benzo[12_b:5,4-b]dioxan-3,3'-吲嗓] A 9.10 Γ-[(2-ketone) Base-1,3-tetrahydroindole _5_yl)methyl]_5 6_dihydrospiro[benzo[l,2-b:5,4-b']di-puffin _3 3, -p?丨哚]-2'(1Ή)-ketone' A 9.11 decyloxy)-yl]-5,6-dihydrospiro[benzo-like seven: 5,4-b]difuran-3,3 '-啕哚]-2'(1,Η), 'A 9.12 14(1-Methyl-1Η-benzopyran-2-yl)methyl]_5,6·dihydrospiro[benzo[1] , 2 7:5,4-b]difuran_3 3'W丨哚]-2'(1Ή)-ketone' Β 9.13 1'-(2Η-benzotriazol-2-ylmethyl)_5, 6-dihydrospiro[benzo[l,2-b:5,4-b']dipyran-3,3'-βbudu]-2,(1Ή)-_ Β 9.14 2-[(2 '-keto-5,6-dihydrospiro[benzo[1,2:7,5,4-b,]-pyran-3,3,-峋哚H,(2,H)-yl)- Benzoic acid A A 9.15 3-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b1]-pyran-3,3'-吲哚H,(2,H)-yl)methyl]benzoic acid '^醢Β 9.16 4-[(2'-keto-5,6-dihydrospiro[benzo[ub:5,4-b] '] - 吱 -3-3, 吲哚]-1, (2·Η)-yl)methyl]benzoic acid methyl A 9.17 1 -Ρ-(benzyloxy)propyl]-5,6-dihydro Snail [benzo[1,2-7:5,4-b']difuran-3,3'-峋哚]-2·(ΓΗ>ketone' Β 9.18 5 yl-l'-[(2R)-four Hydrogenoyl-2-ylmethyl]_5,6-dihydrospiro[benzo[l,2-b:5,47'] cumin _3,3,-m| 哚]-2·( ΓΗ)-ketone ------ Β 9.19 6-fluoro-l'-[(2R)-izg hydrogen hexane-2-ylmethyl]_5,6^^"" Hydrogen snail [benzo [l,2-b : 5,4-bl difuranium]-2'(oxime)-ketone A 9.20 Γ-[2-(2-decyloxyethoxy)ethyl]·2,3-di喃[2,3-g][l,4]benzodioxanthene _8ϋ 哚]-2'(1Ή)-ketone A ---—i ^^^

143924-sp-20091127-6 -1084 - 201020257 ❹

Example No. ------- Compound Name----% inhibition of CYP3A4 9.21 2_ T-based ^decapyridin-2-ylmethyl) snail [Goramic [2,3-f] benzopyrazole -7,3,-吲哚]-2,(1Ή)-ketone A 9.22 丄-LP-fluoro-based small methyl-1Η-imidazole, 2-yl)methyl]_2_indolyl snail [吱 并 [ 2,3-f][l,3]benzoimidazole-7,3,-吲哚]-2'(ΓΗ)-ketone----------- B 9.23 4_ fluorenyl-l '-(((R)-tetrahydrofuran-2-yl)methyl)_4,7-dihydrospiro[benzofuro[5,6-b][l,4]哼耕-8,3,-二Hydroquinone]-2',3(2H)-dione A 9.24 5methyldecidin-2-ylmethyl) snail [吱,[3,2_f] [1,2] benzopyrene _5,3'_p5| 朵]-2'(1Ή)- Stuffed | B 9.25 >Methyl-Γ-(Acridine-3-ylmethyl) snail [Bite 喃[3,2_幻[1 , 2] benzoisoxazole-5,3'-吲哚]-2,(1Ή)-keto B 9.26 3-methyl-r-[(2R),hydrofuran-2-ylmethyl] snail| >Failed and [3,2-f][l,2]benzisoxazole-5,3,-吲哚]-2·(ΓΗ)-ketone A 9.27 Methyl _!|_(tetrahydrogen ·2Η-! Trace 4-ylmercapto) snail [μ benzofuran-3, oxime]-2'(1Ή)-ketone B 9.28 5'6-dimethyl-ι·7-pyridinium_2 _ylmethyl)spirobenzofuran-3,3'-哚]-2'(1Ή)-ketone A 9.29 5-fluoro-6-methoxy-1,-(tetrahydro-2-indole-piperidin-4-ylmethyl)spiro[1-benzofuran-3 ,3,-<哚]-2'(1Ή)-ketone A 9.30 5-1-yl-6-methoxy_1'-{[5-(trifluoromethyl) π π 南_2-yl] Methyl}spiro[1-benzofuran-3,3·-啕哚]-2'(ΓΗ)-keto B 9.31 5,6-difluoro-indole-(acridine-3-ylmethyl) snail [ i•benzofuran-3,3'-^Ι^]-2'(1Ή)-^ B 9.32 5,6-H-Γ-{[5-(trifluoromethyl)pyran-2-yl ]methyl} spiro[1-benzofuran-3,3'-^h^]-2'(rH)-_ B 9.33 6-decyloxy-fluorenyl-(pyridin-2-ylindenyl)-2H -spiro[benzox-3,3'-dihydrop?丨嗓]-2'-嗣A 9.34 6-methoxy-1·-(tetra)pyridin-3-ylmethyl)spiro[1-benzene And furo read-3,3,-啕哚]-2,(1Ή)-ketone B 143924-sp-20091127-6 -1085 - 201020257

Example No. Compound name % inhibition of CYP3A4 9.35 6-Methoxy-indole-(tetrahydro-2H-.sm-4-ylmethyl) snail [ι_benzofuran-3,3'-,?丨哚] -2'(1Ή)-ketooxime 9.36 6-Methoxy-oxime-(tetrahydro-2Η-喊.南-2-ylindenyl) snail [ι_benzofuran-3,3'-啕哚]- 2'(1Ή)-_ A 9.37 Γ-[4-(yloxy)hanyl]-2,3-dihydrospiro[吱,[2,3-g][l,4] stupid and dioxo陆园稀_8,3'_巧丨嗓2,(1Ή)-ketone A 9.38 Γ-[4-(benzyloxy)indolyl]-5,6-dihydrospiro[benzo[i,2_b : 5,4-b']difuran-3,3'-吲哚]-2'(ΓΗ)-_ A 9.39 (8S)-l'-[4-(yloxy)-based]_2,3- Dihydrospirobin β Nanhe [2,3-g][l,4]benzodioxanthene_8,3L 哚哚]_ 2,(1Ή)-ketone A 9.40 {5-[(2 ·-keto-2,3-dihydrospiro[pf-pyrano[2,3_g][i,4]benzodioxanthene-8,3'-吲哚]-1,(2Ή)-曱 曱 ] ] 口 基 基 基 基 基 基 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. 9. ,2-f][l,2]benzoindole p _5,3'-p?丨嗓]-2,(1Ή)- ketone B 9.42 3-mercapto-1'-{[3-( Trimethyl sulfhydryl group > pyridine 2 _ yl] fluorenyl} snail [吱 并 [3, 2-f] [l, 2 Benzoisoxazole _5,3,_啕哚]-2'(1Ή)-keto B 9.43 Γ-[3-(Benzyloxy)propyl]_2,3-dihydrospiro[吱 并[ 2,3-g][l,4]benzodioxanthene_8,3,_,哚]_ 2·(1Ή)-ketone A 9.44 (2'-keto _2,3·dihydrogen Snail [ρ 喃 并 [2,3_g][14] benzodioxanthene-8,3'-吲哚]_ι, (2·Η)-yl)ethyl acetate A 9.45 l'-{[ (4S)-2,2-二基基_ι,3_二氧伍园_4_基]曱基卜 2,3_Dihydrospiro [吱味和[2,3-g][l,4 Benzodioxanthene -8,3·-ρ5丨嗓]-2,(1Ή)-keto B 9.46 6-A>oxydecyloxybenzyl)_2, keto-anthracene Dihydrospiro[1-benzofuran_3,3,_吲哚1_5_carbonitrile B 143924-sp-20091127-6 -1086 - 201020257

Example number Compound name "0ΫΡ3Α4% inhibition^—·· 9.47 6-Methoxy-2'-keto-oxime-(pyridin-2-ylmethyl)-oxime, 2'-dihydrospiro[1 -Benzene oxime-3,3'-吲嗓]-5-carbonitrile Β --- 9.48 6-Fluoro-2匕-yl-Γ-(ρ than bit-2-ylmethyl)·ι' , 2*_diazepine [1-benzopyrene]-5-carbonitrile Β 9.50 6-fluoro-2·-keto-1·-[2-(trifluoromethyl) aryl]_r , 2'_Dihydrospiro[1-benzopyrene-3,3^5 buds]-5-carbonitrile oxime ---- 9.51 6-fluoro-2'-keto-1'-{[ 3-(trifluoromethyl)indole ratio bit_2_yl]methyl}-1',2'-dihydrospiro[1-benzofuran_3,3,_嘀哚]-5-indolecarbonitrile A 9.53 Mercapto 3-[(2'-keto-2,3-dihydrospiro[2,3-g] [1,4]benzodioxene-8,3·-吲哚]-Γ(2Ή)-yl)methyl]benzoate B 9.54 1·-[2-(2-decyloxyethoxy)ethyl]-3-methylspiro[ρ矢喃[ 3, 2 rhyme 1, 2] benzoisoxazole-5, 吲哚]-2, (1Ή)-ketone A 9.55 3-methyl-indole-(3-methylbutyl) snail [吱 并 [ 3,2-f][l,2] benzoisoindole-5,3'-吲嗓]-2·(1Ή)-ketooxime 9.56 3-mercapto-indole-(iv) cultivyl-2-ylmethyl Snail [吱,[3,2-f] [1,2] benzisoxazole-5,3'-吲哚]-2'(ΓΗ)-ketone A 9.57 Γ-[(3-fluoropyridin-2-yl)methyl]-3-indolyl snail [furo[3,2-f][l,2 Benzoisoxazole-5,3·-吲哚]-2,(1Ή)-keto A 9.58 2-[(3-methyl-2'-oxaspiro[furo[3,2〇[1, 2] Benzoisoxazole-5,3'-啕哚]-Γ(2Ή>-yl)fluorenyl]-13-oxazole-4-carboxylic acid methyl ester A 9.59 4-[(2'-keto group -2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3'-呻哚]-1'(2Ή)-yl)methyl Methyl benzoate A 9.60 Γ-[(4-Benzylmorpholine-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,4 Benzodioxanthene-8,3'-蚓哚]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1087 - 201020257

Example No. Compound name CYP3A4 % inhibition 9.64 5,6-Difluoro-indole-(acridin-2-ylmethyl)spirobenzoquinone „Nan-3,3′-嘀哚]-2′(1Ή) -ketone A 9.65 5,6-difluoro-indole-(tetrahydro-2Η- shout-4-ylindenyl) snail [!_benzofuran-3,3'-吲哚]-2Χ1Ή)-ketone A 9.66 2-[3-(Τ-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-啕哚]-Γ( 2Ή)-yl)propyl]-ih-iso, 哚-1,3(2Η>dione B 9.67 Γ-{[5-(estoxy> than biti-2-yl)methyl} snail [吱 并[3,2<][2,1,3]benzo<1 diazole-8,3'-吲嗓]-2,(1'11)-ketone A 9.70 (8S)-l '-[2-(2-Methoxyethoxy)ethyl]_2,3_dihydrospiro-cyano-[2,3-g][l,4]benzodioxanene-8 3, _ 峋哚]-(1Ή)-ketone A 9.71 6'-[2-(2-,methoxyethoxy)ethyl]_2,3_dihydrospiro[V is lost and [2, 3-g][l,4]benzodioxanthene_8,8,_[13] pyrazolo[5,4-eH 哚]-7,(6Ή)-嗣B 9.72 6'-〇 Bipyridin-2-ylindenyl)-2,3-dihydrospiro[p-monopyrano[2,3-g][l,4]benzodioxanthene thinner 'seven,^-serzolo[ 5,4-e]吲哚]-7χ6Ή)-_ B 9.73 4',6'-Dimethoxy- ΐ'_[2-(2-Methoxyethoxy)ethyl]-2,3-dihydrospiroindole[2 3_g][14]benzodioxanthene-8,3· -啕哚]-2,(1Ή)-keto B 9.74 4',6'-dimethoxy-oxime-(10)pyridine-2-ylmethyl)_2,3 dihydrospiro[吱,[2,3 -g][l,4]benzodioxanthene-8,3'-啕哚]-2·(1Ή)-keto B 9.75 6-(2-methoxyethyl-4-oxy)_ι·_ [2_(2_曱ethoxyethoxy)ethyl]spiro[1-benzopyrano_3,3f-indole)-one A 9.76 5-(2-methoxyethyl, yl)_r_[ 2_(2-methoxyethoxy)ethyl]spiro[1-benzofuran_3,3, 卜朵1-2' (THV嗣A 10 1-0荅 基 methyl)_5,6 - dihydrospiro [benzo(1) seven: 5,4 seven] dipyran _3,3'-^丨嗓]-2'(1,1^)-ketone B 143924-sp-20091127-6 - 1088 · 201020257

Example No. ~ ------- % of compound name CYP3A4 inhibits 11 chloro-1,3-inden-5-yl)methyl] snail [吱鸣[2,3-f][l,3 Benzodioxanthene _7,3U?丨嗓2,(1Ή)-ketooxime 11.1 1 -{[2-(-Methylaminopyran-5-yl)methyl} snail [2,3-f][l,3]benzodioxene sulfonate 3, bismuth]-2'(1Ή)-ketone' Β 11.2 Γ-[(2- phloate-4-yl) -1,3-ρ塞峻-5-yl)methyl]spiro[2,3-f][l,3]benzodioxanthene- 7 3,_' L丨哚]- 2'(1Ή)-ketone' Β 11.3 1·-[(2-hexahydroindole-1-yl-13-peak sialyl)methyl] snail [吱,[2,3-f][l, 3] benzodioxolene jy 3, '_ 啕哚]-2'(1Ή)-ketone' Β 11.4 1 -[(2-methoxy-1,3-oxazosin-5-yl) Methyl] snail [吱,[2,3-f][l,3]benzodioxanthene _7 3% 嗓 fly 2|(ΓΗ)-keto oxime 11.5 Γ-(hexahydropyrazole -4-ylmethyl)-5,6-dihydrospiro[benzo-3-[l,2-b . 5,4-b']dipyran-3,3'-t»5 bud]-2 , (1Ή)-class A 11.6 1-{[1-(1-mercaptoethyl)hexahydropyridine_4_yl]methyl b 56_ monohydrospiro [benzo[l,2-b: 5,4 -b']二吱喃_3 3·-ρ?| 哚]-Τ(ΓΗ)-ketone' --- ____ B 11.8 H(l-ethylhexahydropyridin-4-yl)methyl]_5,6-dihydrospiro[benzo[1,2:7:5,4-b']difuran_3,3, -吲, 哚]-2'(1Ή)-ketone------- B 11.10 Γ-[(1-methylhexahydropyridyl)methyl]_5,6-dihydrospiro _ [benzo [l,2-b : 5,4 7'] Difuran-3,3,_Lingduo 2'(1Ή)-ketone----- Β 11.12 3-[(2-mercapto-5,6 - Dihydrospiro [benzo[1,2:7,5,4,7], di-,-3,3'-indole, (2'Η)-yl)methyl], 甲甲酴A 11.13 1 - {4-[5-(Difluoromethyl)-anthracene, 2,4-sodium di-salt-3-yl]-yl}-5,6-dihydrospiro[benzo[i,2_b: 5,4-7 ']二吱喃-3,3'-口?1 嗓]-2'(ΓΗ)-纲~~——一_ ------1 143924-sp-20091127-6 -1089- 201020257

Example No.---------- % inhibition of compound name CYP3A4 11.14 1 _[4-(5-Methyl-1,2,4′′diazol-3-yl)]]5 5_ Diazo snail [benzo[l,2-b . 5,4-b·] dicepan_3 3,βΐ 哚]-2'(1Ή)-ketone' _ A 11.15 Γ-[(5-acridine 4--4-furfuran-2-yl)methyl],5,6-dihydrospiro[benzo[l,2-b:5,4?']dioxan_3,3,·丨嗓丨嗓&gt 2,(1Ή)-keto B 11.16 l'-(4-Pyridin-3-ylindenyl)-5,6-dihydrospiro[benzo[l,2-b. 5,4-b']吱味-3,3'-<»引嗓]·2,(ΐΉ)-_ B 11.17 1 -[U-Fluorobiphenyl-4-yl)methyl]-5,6-dihydrospiro [ Benzo[l,2-b:5,4-b']dipyran-3,3'-吲嗓]_2r(i,H)-keto A 11.18 1'-{2-[5-(trifluoro Mercapto)-1,2,4"diazole-3-(yl)ethyl) snail [furo[2,3-f][l,3]benzodioxanthene-7,3'-吲哚]-2'(1Ή)-嗣B 11.19 4-气基-Γ-{[5-(三败曱基)-ΐ, 2,4-ρ二嗤_3_基] methyl} snail [Nitrate and [2,3-f][l,3]benzodioxanthene-7,3'-choline]-2'(1Ή)-keto B 11.20 4-Alkyl-Γ-[ (5-cyclopropyl-1,2,4-ρ,didentate _3_yl)indolyl]spiro[吱,[2,3-f][l,3]benzo Oxygenene-7,3'-峋哚]-2Χ1Ή)-keto B 11.21 4·-Gas-Γ-{ΐ-[5-(difluoromethyl)-i,2,4-oxadiazole -3-yl]ethyl}spiro[吱,[2,3-f][l,3]benzodioxanthene-7,3'-吲哚]-2,(1Ή)-嗣B 11.22 1'-{[5-(Difluoromethyl)4,2,4-oxadiazol-3-yl]indolyl} snail [吱,[2,3-f][l,3]benzo Dioxynene _7,3,-吲哚]-2'(1Ή)-keto B 11.23 Γ-[(5-Terti-butyl 4,2,4-oxadiazol-3-yl)anthracene Alkyl] snail [, succinyl[2,3-f][l,3]benzodioxanthene-7,3,-吲哚]-Ζ(ΓΗ)-ketone B 11.24 ^[(5-ring Propyl-1,2,4-oxadiazol-3-yl)methyl]spiro[吱,[2,3〇[1,3]benzodioxanthene-7,3·-吲哚]-2'(ΓΗ)-ketone B -1090- 143924-sp^20091127-6 (8) 201020257

Example No. Compound name CYP3A4 % inhibition 11.25 4-Chloro-indole-{[5-(1-methylethyl)-l,2,4-p-di-salt-3.yl]methyl} snail [吱Methane [2,3-Hungry 1,3] benzodioxolanes-7,3·-啕哚]-2'(1Ή)-keto B 11.26 Γ-{[5-(1-methyl B ))-l,2,4-吟二峻-3-yl]methyl} snail [吱,[2,3-ί][1,3]benzodioxanthene-7,3,-啕哚]ΚΙΉ)-ketone B 11.27 l'-[3-(5-Methyl-l,2,4-oxadiazol-3-yl)-yl]-5,6-dihydrospiro[benzo[ l,2-b : 5,4-b·]difuran-3,3'-rhodium]-2'(1Ή)-keto B 11.28 1'-{3-[5-(trifluoromethyl)- 1,2,4-oxadiazol-3-yl]-yl}} 5,6-dihydrospiro[benzo[i,2-b:5,4-b']dioxan-3,3, -吲哚]-2·(1Ή)-keto B 11.29 Γ-[4-(5-fluorenyl-4Η-1,2,4-triazol-3-yl)benzyl]-5,6-diindole Snail [benzo[l,2-b:5,4-b'] dioxin--3Χ 哚]-2·(1Ή)-keto B 11.30 2-[(2'-keto-5,6-di Hydrogen snail [stup [1,2 7:5,4-b,]difuran-3,3'-吲哚]-1'(2Ή)-yl)indenyl]benzoic acid A 11.31 4-[(2 '-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]difuran-3,3'-«1 哚]-1,(2Ή)-yl )methyl]benzamide A 11.33 Ν'Ν-dimercapto_5-[(2, fluorenyl-2,3-dihydrospiro[吱,[2,3-lu][1,4]benzodioxanthene] 8,3'_>15丨)1 to]_1'(2Ή)-yl)methyl]furan-2-carboamine B 11.34 Γ-(3-hydroxypropyl)-5,6-dihydrospiro [Benzo[i,2-b : 5,4-b,] dipyran-3,3'-吲嗓]-2,(1Ή)-_ A 11.35 2,-ketohydrofuran ]_r,2,,5,6_ Tetraspira [Benzo[l,2-b: 5,4-1>'] Dipyran-3,3.51 哚]-4'-carbonitrile A 11.37 4 ·-[(Dimethylamino)methyl; mR)·tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzophenoline, 2-7:5,4-b']difuran-3, 3·-吲哚]-2'(i,h)-ketone A

143924-sp-20091127-6 1 1091 · 201020257 1'-{[3-(Trifluoromethyl]>Bit_2_yl] fluorenyl}_2,3_Dihydrospiro [味喃而幻[^] Benzodioxanthene-7,3·-β哚]-2'(1Ή)-one; 6-methoxy_144_methoxy-yl)_2, shoulder group Γ, 2, _ Cyclone benzophenone-flavor-3 啕哚]-5-phthalonitrile; 6-methoxy-2,-yl-i, 7-buty-2-ylmethyl)_Γ,2·_dihydrospiro [μ笨和福味-3,3,丨哚丨哚]-5-carbonitrile; 6-fluoro-2,-keto-1,-(10)pyridine-2-ylmethyl)-1,,2, - dihydrospirobenzofuran_3,3,_吲哚]-5-phthalonitrile;

6-Fluoro-2'-keto-l,-[(2R)-rahydrofuran-2-ylindenyl hydrazino, 2,_dihydrospiro to benzofuran-3,3'-吲哚] -5-carbonitrile; 6-fluoro-2,-keto-rR(trifluoromethylindenyl)-indole, 2,-dihydrospiro[indolobenzofuran-3,3 W丨哚]-5- Carbonitrile; 6-fluoro-2'-keto-oxime-{[3-(trifluoromethyl)p-bito-2_yl]methyl}p 2,_dioxane [1 benzofuran- 3,3'-啕哚]-5-carbonitrile; Γ-(4-bromobenzyl)-5,6-difluorospiro[1-benzofuran_3,3,-ρ5丨哚]-2 , (l,H)-ketone; 5.6-difluoro-l'-(3-methylbutyl)spiro[1_benzofuran_3,3U5丨哚]_2, (ιή) ketone; 5.6-difluoro - Γ々 啶 冬 冬 ) ) ) ) [丨 苯 benzofuran _3, 3, _ 吲哚] _2, (ι ή) ketone; 5 '6-difluoro-1 '- (tetrahydro-2 Η - Piperazin-4-ylindenyl)spiro[μbenzofuran_3,3,_(f)哚>2'(1Ή)-one; 1 _{[5-(oximeoxy)pyridin-2-yl曱 } } 螺 吱 吱 以 以 以 以 以 以 以 以 以 以 以 以 以 以 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯-(2-decyloxyethoxy)ethyl]spirobenzofuran-3,3·-called 丨哚]-2'(1Ή)-one; 5-(2-decyloxyethoxy) -142-(2-methoxyethoxy)ethyl] Stupid and furosemide 143924-sp-20091127-1 -111 - 201020257

Example No. Compound name % inhibition of CYP3A4 11.38 4'-(tetrahydropyrrolidinyl)>r_[(2R)_tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[i,2- b : 5,4-b,]difuran-3,3·-啕哚] A 11.39 4'-Amino-l'-[(2R)-tetrahydrofuran-2-ylmethyl]_5,6-dihydrogen Snail [benzo[l,2-b:5,4-b']dioxan.-3,3^51 哚]-2·(1Ή)-keto B 11.41 Γ-[(4 dimethyl kefu)啉-2-yl)methyl]_5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran_3,3,_啕哚]-2'(ΓΗ) -keto B 11.42 l'-{ [4-(1-mercaptoethyl)moffin 2 —yl]fluorenyl}-5,6-dihydrospiro [stupid [l,2-b: 5, 4-b'] Dipyran-3,3,-β丨哚]-2'(1Ή)-keto B 11.43 Γ-Methyl-5,6-dihydrospiro [Benzene like 7:5,4_b. Difuran-3,3'-(5)哚]-2,(1Ή)-ketone A 11.44 Γ-[4-(1Η-tetrazol-5-yl)benzyl]-5,6-dihydrospiro[benzene And [l,2-b: 5,4-b']difuran-3,3,-throindole-2,(1'11)-one B 11.45 Γ-(3-hydroxybenzyl)-5, 6-Dihydrospiro[benzo[i,2-b : 5,4-7,]difuran-3,3'-吲哚]-2'(1Ή)-one B 11.46 Γ-(4-morphine 4-ylbenzyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran_3,3 ,_啕哚]-2,(1Ή)-keto B 11.47 6-Amino-r-[(2R)-tetrahydrofuran·2_ylmethyl]spirofl_benzoxanthene-5-3'-p卜朵]-2'(1Ή)-keto B 11.48 Ν-{2'-keto-r-[(2R)-tetrahydrofurazan-2-ylmethyl]_Γ, 2, _ a snail [ 1-benzopyran-3,3'-p?丨嗓]-6-yl}methyl sulfonamide A 11.49 6-carbyl-1·-(3-methylbutyl)spiro-benzo吱 _3 3, _ 吲哚] - 2 '(1 Ή)-ketone ' B 11.50 6-Alkyl-1·-(3-methylbutyl)-5-(trifluoroethenyl)spiro π_ benzene And furan-3,3'-峋哚]-2·(1Ή)-_ B 11.52 6-[(3R)-izg hydrogen itbilo-3-ylamino]trifluoromethyl)anthrene-11 South-2 -yl]methyl}spiro[1-benzopyranin_3 3'-啕哚]-2 丫1Ή)-ketone' B 143924-sp-20091127-6 -1092 - (S) 201020257

Example No. Compound name % inhibition of CYP3A4 11.53 6-trans-yl-r-[(2R)-ii9hydrofuranylmethyl]spiro[1-benzofuran-3,3.卜朵]-2'(1,H)-keto A 11.54 6-0 methylethoxy)-l'-[(2R)_tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran_ 3,3,-吲哚]-2,(1Ή)-ketone A 11.56 6-[(3S)-Tetrahydropyrrole-3-yloxytetrahydrofuran-2-ylmethyl]spiro[1_benzofuran_ 3,3,_p?丨哚]-2'(1Ή)-ketohydrochloride A 11.58 6-[(3R)-w Hydropyrrole-3-yloxy]_14(2R)_tetrahydrofuran-2-yl Snail [1-benzofuran_3,3,_钊哚]-2'(1Ή)-ketohydrochloride A 11.60 1'-[(211)-tetrahydrofuran-2-ylmethyl]spiro[benzene And [i,2-b : 5,4-b]difuran-3,3W丨哚]-2',5(1Ή,6Η)-dione A 11.61 Γ-(tetrahydropyrrol-3-ylmethyl -5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2'(1 ugly)-keto A 11.62 N- (l-methylethyl)-3-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3' - 哚 哚]-Γ(2Ή)-yl) methyl]tetrahydropyrrole-1-carboxyguanamine B 11.63 1·-[(4-methylhexafluoropyran-1-yl)methyl] snail [bite M-[2,3-f][l,3]benzodioxolene-7J-吲哚]-2'(1Ή), keto hydrochloride B 11.64 (3S)-6-decyloxy- 5-methyl-indole-[(4-mercaptohexahydropyridinyl)indolyl][1] -Benzo-puffrano-3,3'-吲嗓]-2,(1Ή)-ketohydrochloride A 11.65 (3R)-6-methoxy-5-methyl-oxime-[(4-A Hexahydropyridin-1-yl)methyl]spiro[1-benzopyran-3,3·-吲嗓]-2'(1Ή)-ketohydrochloride B 11.62 (3S)-r-[ (2R)-rahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-anthracene] _ 2'(1Ή)-ketone A 11.67 (3R)-r-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4 -b·]difuran-3,3·-吲哚]_ 2'(1Ή)-ketone A 143924-sp-20091127-6 -1093 - 201020257

Example No. Compound name CYP3A4 % inhibition 11.68 (3R)-r-[(2S)-tetrahydrofuran-2-ylindenyl]-5,6-diaza snail [stupid [l,2-b: 5,4- b']difuran_3,3'-β丨哚]-2'(1Ή)-ketooxime 11.69 (3S)-1'-[(2S)-tetrahydrofuran-2-ylmethyl]-5,6- Dihydrospiro[benzo[l,2-b:5,4-b']difuran_3,3,-closed]-2"(1Ή)-ketone A 11.70 1 - {[(2S)-1 -mercapto-5-_yltetrahydro-p-bi-2-yl]methyl}-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3 , 3'-mouth bow 1 哚]-2'(1Ή)-keto B 11.71 14(3-mercapto-2-keto-1,3-tetrahydroxazole-5-yl)indolyl] snail [吱喃[2,3-f][l,3]benzodioxolene^]-2'(rH)-ig B 11.72 1·-{[5-(trifluoromethyl)-1,2 , 4-oxadiazol-3-yl]fluorenyl} snail [ρofrano[2,3-f][l,3]benzodioxol-7,3·-吲哚]-2Χ1Ή )-keto B 11.73 N-isopropyl-3-[2-(2·-oxaspiro[吱,[2,3-f][l,3]benzodioxol-7,3|| -吲哚]-1'(2 ugly)-yl)ethyl]hexahydropyridine-1-carboxyguanamine B 11.74 5-[(2'-oxaspiro[吱,[2,3-f][l , 3] benzodioxolone-7,3-?-duo]-Γ(2Ή)-yl)methyl], thiophene-3-beta B 11.75 2'-keto-anthracene, 2'-dihydrospiro[吱,[2,3-phan [1,3]benzodioxol-7,3'-吲哚]-71-曱Nitrile B 11.77 Γ-Methyl-fluorenyl-keto-1',2,2',3-tetrahydrospiro[,,[2,3-phan [1,4]benzodioxanthene-8 ,3'-吲哚]-4'-carboxylic acid A 11.78 3 odor base than bit-2-yl)methyl]-2,3-diaza snail [biting and [2,3-g][l, 4] benzodioxanthene-8, Γ-茚]-2'(3Ή)-ketone A 11.79 3'_{[3-(oxasulfonyl oxaridin-2-yl)methyl}-2 ,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene•8,1'-茚]-2'(3Ή)-ketone A 143924-sp- 20091127*6 -1094 - 201020257

Example No. 11.80 % inhibition of compound name CYP3A4 2_[(2^& _2,2,,3,3,-tetrahydrospiro[2,3-g][l,4] soil open dioxane Terpene _8,1,-茚]·3,_yl} fluorenyl; 1pyridine-3-carbonitrile A 11.81 11.83 {[3 fluoromethyl) ρ pyridine _2 yl] methyl}_2 3二f螺[唉,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]_2·(ι,Ην ketone A 1 -[3: armor Base 4,2,4′′ oxazol-3-yl)]]],] 2,3-di snail [吱,[2,3-g][l,4]benzodioxanthene- 8,3'-啕哚]_2'(ι·η)-net B 11.84 1'-Κ-(5-methyl_1,2,4′′ diazole-3-yl) Yuji]-2, 3-dihydrospiro [c-buto[2,3-g][l,4]benzodioxanthene-8,3,吲哚]_2, (i,h)-keto A 11.85 6-( 5-mercapto-i,2,4-oxadiazole _3_yl)-1,-(pyridin-2-ylindenyl)spiro[1-benzofuran_3,3,-吲哚]-2 '(1Ή)-net A 11.86 3-[(2'-_ yl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 ,3,-吲哚]-Γ(2Ή)-yl)indenyl]benzoic acid A 11.87 4_[(2:,yl 2,3-dihydrospiro[吱,[2,3_g][1,4 Benzodioxanthene-8,3·-啕哚]-1,(2Ή)-yl)A Benzoic acid A 11.90 Γ-{[5-(Trifluoromethyl) 4,2,4-oxadiazol-3-yl]indolyl}-2,3-dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-keto B 11.92 1'-{[5-(trifluoromethyl)·ι , 3,4-oxadiazol-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8, 3·-吲哚]-2·(1Ή)-_ A 11.94 Ν-{3-[(2^-keto-2,3-di-argon snail [吱,[2,3-g][l,4 Benzodioxanthene-8,3'-indole]-indole (2Ή)-yl)indenyl]phenyl}-calcined indoleamine B 11.95 1·-[(1-oxopyridine-2- Methyl]-2,3-dihydrospiro[n-[2,3-g][l,4]benzodioxol-8,3. Bow | 哚]-2'(1Ή)-ketone A 143924-sp-20091127-6 • 1095 - 201020257 Example No. Compound name CYP3A4 % inhibition 11.97 Γ-[(3-Aminopurine-2-yl) fluorenyl ]-2,3-dihydrospiro[ντ矢喃[2,3-g][l,4]benzodioxanthene_8,3,_哚哚]-2'(1Ή)-ketone Hydrobromide hydrazone 11.98 Ν-{2-[(2'-keto-2,3-dihydrospiro[bit, benzo[2,3_g][i,4] benzodioxanthene -8, 3'-吲嗓]_ι'(2Ή)-yl)methyl]ρ-pyridin-3-yl}methanesulfonamide Β 11.99 Γ-(hexahydropyridine~4_ylmethyl)-2,3-di Hydrogen snail [吱,[2,3-g][l,4]benzodioxolene _8,3·-吲哚]-2'(1Ή)-one hydrochloride A 11.100 Γ-{ [1-(1-decylethyl)hexahydropyridin-4-yl]fluorenyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodiox Lumene-8,3'-啕哚]-2·(1Ή)-ketohydrochloride B 11.101 methylhexahydropyridin-4-yl)methyl]-2,3-dihydrospiro[吱[2,3-g][l,4]benzodioxanthene _8,3,_ 吲哚]-2'(1Ή)-ketohydrochloride A 11.102 1 -(Hofolin-2- Methyl)-2,3-dihydrospiro [biting and [2,3-g][l,4]benzodioxanthene -8,3'-啕哚]-2'(1Ή) -ketone A 11.103 Γ-{ [4-( 1-mercaptoethyl)fosfolin-2-yl]methyl b 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 ,3'-啕哚]-Τ(ΓΗ)-ketooxime 11.104 Γ-[(4-Methylorfos-2-yl)indenyl]-2,3-dihydrospiro[, 3-g][l,4]benzodioxanthene_8,3,-fluorenone oxime 11.106 (8S)-r-{[(2SH-methylmorpholin-2-yl)methyl }-2,3-Dihydrospich-[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-ketone A 11.107 Γ-{[3-(trifluoromethyl)pyridin-2-yl]methyl} snail [bito-[3,2-e][2,l,3]benzoxadiazole-8,3 ·-啕哚]-2·(1Ή)-ketooxime 11.108 6-Gas-anthracene-{[3-(trifluoromethyl)-pyridin-2-yl]methyl}-2,3-dihydrospiro [吱吱[3,2-f][l,4]benzodioxanthene-9,3'-吲哚]-2'(1Ή)-ketone A 143924-sp-20091127-6 . 〇96-

(S 201020257

e

Example No. ------- Compound name ^ΥΡ3Α4^Γ % inhibition~--~--- A 11.109 Γ-{[3-(trifluoromethylcyclopyridine_2_yl)methyl snail [biting And [3,2-f][l,4]benzodioxanthene-9,3'-吲哚]-2'(1Ή)-one 11.110 14[5-(difluoromethyl)pyran _2_yl]methyl}-2,3ΤΓϊ~ snail [吱,[2,3-g][l,4]benzodioxanene-8,3'-吲哚]-2' ( 1Ή)-ketone~~--- B 11.111 5,6-difluoro-indole-(hexahydropyridin-4-ylmethyl)spiro[1-benzene^~furan-3,3·-»5丨哚] -2'(1Ή)-ketohydrochloride-B 11.112 5,6-'-D-methylhexachloro-p-butyt-4-yl)methyl]spiro[1-benzofuran_3,3.丨哚]-2·(1Ή)-ketohydrochloride~---~~~- B 12 Ν-(cyclohexylmethyl)_3-[(2'-keto-5,6-dihydrospiro) [Benzene~~[1,27:5,4-b']difuran-3,3,-啕哚]-Γ(2Ή)-yl)methyl]benzamide-----^ B 12.1 Ν-(2-decyloxyethyl)_3-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3 ,3W丨哚]-1·(2Ή)-yl)methyl]benzamide------- B 12.2 N-hexyl-N-mercapto-3-[(2·-keto-5 ,6-dihydrospiro[benzo[l,2,b:5,4-b.]difuran-3,3匕口?|哚Η,(2Ή)-yl) fluorenyl]benzamide- —— B 12.3 仏 仏 丨 丨 丨 丨 叹 酮 酮 ketone ketone ^ iso-dihydrospiro-[i,2-b: 5,4-b']difuran-3,3'-啕哚]-Γ (2Ή)-yl)methyl]benzamide-5 12.4 Ν-(2,4-dimethylphenyl)-3-[(2'-keto-5,6-dihydrospiro[benzo[ l,2-b : 5,4-b]difuran-3,3'-<哚]-WH)-yl)methyl]benzoguanamine B 12.5 3-[(2'-keto-5 ,6-dihydrospiro[benzo[l,2-b:5,4-7]difuran-3,吲哚]-Γ(2Ή)-yl)methyl]-N-(2-phenylpropane) Benzomethane B 12.6 N-[(1S)-1-cyclohexylethyl]-3-[(2·-keto-5,6-dihydrospiro[benzo [l,2-b: 5,4-difuran-3,3'-(4)哚]-indole (2Ή)-yl)methyl]benzamide B l43924-sp-2009ll27-6 -1097 - 201020257

Example No. Compound name CYP3A4 % inhibition Β AB 12.7 N-[(1R)-1-cyclohexylethyl]-3-[(2'-keto-5,6-dihydrospiro[本和[l,2 -b . 5,4-b']Two-bite β South_3,3'-u5丨嗓]_Γ(2Ή)-yl)methyl]benzamide 0.28 Ν-(4-ethylphenyl) -2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-,哚]-1, ( 2Ή)-yl) fluorenyl]benzamide 12.9 Ν-(2-ethylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b] : 5,4-b']二吱口南-3,3'-令朵]-1,(2Ή)-yl) fluorenyl]benzamide 0.110 Ν-(2,4-dimercaptophenyl )-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']didentate-3,3'-bow]- 1'(2Ή)-yl)mercapto]benzamide-5 12.11 Ν-(2-methoxyphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l ,2-b : 5,4-b·]di-n-but-3,3'-吲哚]-ΐ,(2Ή)-yl)methyl]benzamide-5 12.12 Ν-(2-fluorophenyl )-2-[(2·-keto-5,6-dihydrospiro[benzo-~[l,2-b : 5,4-b']difuran-3,3'-吲哚]- ΐ,(2Ή)-yl) fluorenyl]benzamide B 12.13 Ν-(3-phenylphenyl)-2-[θ-keto-5,6-dihydrospiro[ And [l,2-b : 5,4-b']difuran-3,3'-called | 哚]-ΐ·(2Ή)-yl)methyl]benzamide B 12.14 Ν-(3- Fluoro-2-methylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxan-3 ,3W|ρ朵]-Γ(2Ή)-yl)indolyl]benzamine B 12.15 Ν-heptyl-2-[(2'-keto-5,6-dihydrospiro[benzo[ub][ub : 5,4-b']difuran-3,3'-4丨哚]-Γ(2Ή)-yl)indenyl]benzamide B 12.16 Ν-(2-acetobenzyl)-2-[ (2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-啕哚], γ(2Ή)-yl) Benzyl]benzamide-5 12.17 Γ-[2-(hexahydropyridin-1-ylcarbonyl)-yl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b ']Difuran-3,3^5丨哚]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1098 - 201020257 Example No. Compound name CYP3A4 % inhibition 12.18 N-butyl-2-[ (2'-keto-5,6-dihydrospiro[benzo[i,2_b:5,47']difuran-3,3Wbdu]-Γ(2Ή)-yl)methyl]benzamide Indoleamine 1 ~~~ _ Β 12.19 Ν-(3-methylphenyl)-2-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5' 4-b'] dioxin-3,3'-^丨哚]-1, (2Ή)-yl) Benzoamine------- Β 12.20 Ν-(2-fluoro-5-methylphenyl)-2-[(2·-keto-5,6-dihydrospiro[benzene] And [l,2-b : 5,4-b·]difuran _3,3,- 哚 哚]_ Γ(2Ή)-yl) fluorenyl]benzamide Β 12.21 Ν-(2,3- Monomethylphenyl)-2-[(2^嗣基·5,6-dihydrospiro[本弁[l,2-b · 5,4-b·]二咬喃-3,3W卜朵] -Γ(2Ή)-yl)methyl]benzamide oxime 12.22 2-[4-(4-methoxyphenyl)ethyl]-2-indolyl-keto-5,6-dihydrospiro[benzo [l,2-b : 5,4-b']difuran-3,3'-thirsty]-1'(2Ή)-yl)methyl]benzamide Β 12.23 Ν-(3-气爷))-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-ΐ '(2Ή)-yl) fluorenyl]phenylamine oxime 12.24 Ν-[2-(4-phenylphenyl)ethyl]keto-5,6-dihydrospiro[benzo[l,2-b : 5,4-b']Dop-p-β-Nan-3,3'-«»5-Puo]-Γ(2Ή)-yl)methyl]benzamide Β 12.25 Ν-(2-methoxybenzene -4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,31.吲哚]-1, (2Ή)-yl)methyl]benzamide A 12.26 4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Mutter -3,3'-吲哚]-1'(2Ή)-yl)methyl]-N-[2-(trifluoromethyl)phenyl]benzoguanamine B 12.27 4-[(2'-ketone) -5,6-dihydrospiro[benzo[l,2-b: 5,47']di-n--3,3'-吲哚]-Γ(2Ή)-yl)methyl]-N -Phenylbenzamide A 12.28 Ν-mercapto-4-[(2'-keto-5,6-dioxaspiro[benzo[l,2-b:5,4-b']difuran ·3,3'-吲哚]-1'(2Ή)-yl)methyl]benzamide Β 143924-sp-20091127-6 -1099- 201020257

Example No. Compound name CYP3A4 % inhibition 12.29 N-(2-fluorophenyl)-4-[(2'-fluorenyl-5,6-dihydrospiro[benzo[l,2-b: 5,4- b']difuran-3,3,-啕哚]-1,(2Ή)-yl) fluorenyl]benzamide A 12.30 4-[(2'-keto-5,6-dihydrospiro[ Benzo[l,2-b: 5,4-b']disin-3,3·-吲哚]-Γ(2Ή)-yl)indolyl]-N-(2-purine-2- Benzyl)benzamide-5 12.31 4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-b: 5,4-b']di-p--3 ,3'-啕哚]-Γ(2Ή)-yl)indolyl]benzamine B 12.32 Ν-(2,3-dihydro-1Η-茚-5-yl)-4-[(2,- Keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']di-n--3,3'-ρ5 noisy]-1'(2Ή)-yl)曱Benzoylamine A 12.33 Γ-[4-(morpholine-4-ylcarbonyl)-yl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b· ]二咬°南-3,3W| 哚]-2Χ1Ή)-keto B 12.34 (2-ethylphenyl)-4-[(2-keto-5,6-dihydrospiro[benzo[1] ,2-b : 5,4-b']difuran-3,3,-啕哚]-Γ(2Ή)-yl)methyl]benzamide B 12.35 Team (2,6-Dimethylbenzene) -4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-吲哚]-Γ (2Ή)-曱]]benzimidamide B 12.36 Ν-(3-fluorophenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4] -b']difuran-3,3,-吲哚]-1,(2Ή)-yl)methyl]benzamide A 12.37 Ν-(2,4-dimercaptophenyl)-4-[ (2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-啕哚Η'(2Ή)-yl) A Benzoylamine A 12.38 4-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-ty]difuran-3,3'-啕哚]-Γ(2Ή)-yl) fluorenyl]-N-(pyrimidin-2-ylmethyl)benzamide-5 12.39 N-ethyl-4-[(2, keto-5,6- Dihydrospiro[benzo[l,2-b:5,4-b]difuran-3,3'-吲哚]-indole (2Ή)-yl)methyl]benzamide-5 143924-sp- 20091127-6 -1100· 201020257

φ Instance number ----- Compound name CYP3A4% inhibition 12.40 Ν-(2-methoxyethyl)-4-[(2'-_ _5 table dihydrospiro [benzo[l,2- b : 5,4-b']二ρ失喃-3,3'-帝朵i_i,(2,HV-based)methyl]benzamide) A 12.41 N-(2:ethoxyethyl) -4-[(2,-keto_5,6-dihydrospiro[benzo[l,2-b. 5,4-b]-methane)-ΐ'(2Ή)_yl)methyl Benzalamine B 12.42 N-cyclobutyl-4-[(2-keto-5,6-dihydrospiro[benzo[7:5,4-b']difuran-3,3- Mouth 5丨哚]-1(2H)-yl)methyl^]clumamine B 12.43 4-[(2'-keto-5,6-di-argon][benzo[1,2:7:5, 4-1>'] Diterpene-3,3,,丨哚Η'(2Ή)-yl)methylpyrazol-2-ylbenzamide A 12.44 Team (3-indolyl-2-mercapto Phenyl)-4-[(2'-c-yl-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxan-3,3'-啕嗓] _ 1 '(2Ή)-yl)methyl]benzamide A 12.45 Ν-(2-ethylbutyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[ l,2-b : 5,4-b']difuran-3,3·-吲哚]-1,(2Ή)-yl)methyl]benzamide A 12.46 2-(2'-keto -5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxan-3,吲哚]-Γ(2Ή)-yl)Ethylamine A 12.47 Ν-(4-ethylphenyl)-2-(2'-keto-5,6-dihydrospiro[benzo[l,2 -b : 5,4-b,]difuran-3,3,-吲哚]-1,(2Ή)-yl) acetamamine A 12.48 Ν, Ν-diethyl-2-(2'-one -5,6-dihydrospiro[benzo[l,2-b:5,4-b丨]difuran-3,3W|哚]-Γ(2Ή)-yl) acetamamine A 12.49 Ν- (3,3-dimethylbutyl)-2-(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,吲哚]-Γ(2Ή)-yl)acetamide-------- B 12.50 N-[3-(l-methylethoxy)propyl]-2-(anthracene-keto- 5,6-dihydrospiro[benzo[Ub:5,4-b.]difuran-3,3'-indole]-indole (2Ή)-yl)acetamidamine B ——. 143924-sp- 20091127-6 -1101· 201020257 -3-3,3'-啕哚]-2'(ΓΗ)-ketone; Γ-{[3-(trifluoromethyl)acridin-2-yl]indenyl} snail [吱 并[3,2-e][2,l,3]benzoxadiazole-8,3'-吲哚]-2'(1Ή)-one; 1'-{[3-(trifluoro Methyl aridin-2-yl]methyl}-2,3-dihydrospiro[p-benzobenzodioxene-9,3'-吲哚]-2·(1Ή)-one; 5.6 - -Fluoro-1 -(hexazalobazin-4-ylindenyl)spiro[1-benzopyrano 3,_ 4丨哚]-2'(1Ή)- Hydrochloride; 5.6-difluoro-indole-[(1-mercaptohexahydropyridin-4-yl)indolyl]spiro[1-benzopyrano_3,3,old oxime]-2'(1Ή) -ketohydrochloride; Ν\6-dihydroxy-hydrazine-(4-methoxybenzyl>2'-keto-oxime, 2·-dihydrospiro[μbenzopyran--3,3 '-啕哚]-5-carboxy quinone imine amide; 6-hydroxy-fluorenyl-keto-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-indole, 2,-dihydrospiro Benzofuran-3,3'-吲哚]-5-carbonitrile; 6-hydroxy-2'-keto-oxime-[2-(trifluoromethyl)henyl]-oxime, 2·-dihydrogen Snail [ι_benzo bite. South-3,3'-thirty 哚]-5-phthalonitrile; Γ-[(5-alkyl-2-ρ塞 yl) fluorenyl]-5-(6-fluorenyl ρ ratio -3- Alkyl snail [L stupid sulphur-3,3'- sorghum]-2Χ1Ή)-ketone; 5.6--gas-1 -{4-[(3R)_tetrazine p ratio π each _3-amine Base] Hanji snail []__ stupid and taste. South-3,3'-throat]-2'(1|11)-ketohydrochloride; 9-fluoro-2,3-dihydro-spiro[[,3-g][l , 4] benzodioxanthracene _8 3,(9) 哚]-2'(1Ή)-one; 7,8-dihydro-6Η-spiro [bito-and-[2,3-g] octa-ene- 3,3,-port 5丨嗓]-2'(1Η)-ketone; 6-chloro-2,3-dihydrospiro[吱,[3,2-f][l,4]benzoic Oxygen, 哚 哚]-2'(1Ή)-ketone; 143924-SP-20091127-1 201020257

Example No. Compound name CYP3A4 % inhibition 12.51 2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-1'(2Ή)-yl)-N-propylacetamide oxime 12.52 Ν-methyl-2-(2'-keto-5,6-dihydrospiro[benzo[1,2 VII: 5,4-b']difuran-3,3'-吲哚]-Γ(2Ή)-yl)-oxime-phenylacetamide oxime 12.53 Ν-(2,5-dimethylphenyl )-2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-W 哚]-Γ(2Ή )-yl) acetamamine A 12.54 Ν-(2,4-dimethylphenyl)-2-(2·-keto-5,6-dihydrospiro[benzo[1,2-b: 5 ,4-b']difuran-3,3·-啕哚]-1·(2Ή)-yl)acetamidamine B 12.55 Ν-(2,3-dimethylphenyl)-2-(2' -keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-蚓哚]-indole (2Ή)-yl)acetamide B 12.56 Ν-(2,6-Dimethylphenyl)-2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Furan-3,3,-哟哚]-Γ(2Ή)-yl)acetamidamine B 12.57 Ν-methyl-5-[(2'-oxaspiro[吱,[2,3-f][l ,3]benzodioxanthene-7,3'-吲哚]-1|(2 condition)-yl)methyl]-2-(trifluoromethyl)pyranyl-3-carboxyguanamine B 12.58 5-[(2'-oxaspiro[furo[2,3-f][l,3] benzodioxol-7,3·-啕哚Η'(2Ή)-yl) Mercapto]-2-(trifluoromethyl) succinyl-3-carboxamide A 12.59 Ν, Ν-dimethyl_5-[(2'-oxaspiro[吱,[2,3-f]] [l,3]benzodioxanthene-7,3'-吲哚]-1,(2'-indenyl)indenyl]-2-(trifluoromethyl)p lost"South_3_ Rebel amine B 12.60 4-[(2·-Net-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3' -吲哚]-1,(2Ή)-yl) fluorenyl] benzoic acid B 12.61 Η(2'-keto-2,3-di argon [吱,[2,3-g][l , 4] benzodioxanthene-8,3'-吲哚]-1, (2Ή)-yl) fluorenyl] benzoguanamine B 143924-sp-20091127-6 -1102- (S) 201020257

Example No. Compound name CYP3A4 % inhibition 12.62 N,N-dimercapto-3-[(2·-keto-2,3-dihydrospiro[唉,^^[2,3-g][l,4 Benzodioxanthene _8,3,-吲哚]-Γ(2Ή)-yl)mercapto]phenylamine oxime 12.63 Ν-mercapto-2-[(2'-keto-2 ,3-dihydrospiro[吱〇南和[2,3_g] [1,4]benzodioxanthene_8,3·-吲哚]-1'(2Ή)-yl)methyl]pyridine -3-carboxyguanamine A 12.64 Ν-(2-aminoethyl)-2-[(2'-keto-2,3-dihydrospiro [scream and [2,3-g][l, 4] benzodioxanthene _8, 3l 哚Γ 哚Γ (2 Ή)-yl) methyl] p than -3- 竣 胺 amine dihydrochloride B 12.65 Ν-(2-fluorophenyl)- 4-[(2'-Mentyl-2,3-dihydrospiro[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-Γ (2Ή)-yl) fluorenyl]benzamide A 13 5-[(2·-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]吱 -3-3,3'-吲嗓]-1·(2Ή)-yl)methyl]pyran-2-t-acid A 13.1 Ν,Ν-dimethyl-5-[(2'-keto- 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3·-翊哚]-Γ(2Ή)-yl)methyl]furan-2- Carboguanamine Β 13.2 Ν-methyl-5-[(2·-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b·]difuran-3,3'-啕哚]-1·(2Ή)-yl)methyl]furan-2-carboxyguanamine Β 13.3 2-[(2·-keto-5 ,6-dihydrospiro[benzo[1,2-b: 5,4-b,]difuran-3,3'-啕哚]-Γ(2Ή)-yl)methyl]-i,3- Oxazol-4-carboxycarboxamide A 13.4 Fan dimethyl dimethyl snail-keto group ^ each dihydrospiro drop [l,2-b: 5,4-b·] biceps-3,3'- 〇5h1](2Ή)-yl)methyl]-1,3-ρ-salt-4-indole A 13.5 Ν-cyclopropyl-2-[(2·-oxo[[ And [2,3-f][l,3]benzodioxanthene-7J-啕哚Η'(2Ή)-yl)methyl]-1,3- indole-4-sulfoximine 13.6 N-(l-methylethyl)-2-[(2'-oxaspiro[吱,[2,3-f][l,3] benzodioxolan-7,3^5 |,]-Γ(2Ή)4)Τ base]-1,3-ρ#嗤-4-竣醯amineΒ 143924-sp-20091127-6 -1103· 201020257

Example No. Compound name CYP3A4 % inhibition 13.7 Phenyl)-2-(2'-keto-2,3-dihydrospiro[p-β-N-[2,3-g][l,4]benzoic Oxalene _8,3'_ρ§丨哚]-1'(2Ή)-yl) acetamamine A 13.11 Ν-[3-(2'-keto-5,6-dihydrospiro[benzo [1,2 7:5,4-b,] Difuran-3,3'-啕哚]-1'(2Ή)-yl)propyl](trifluorodecyloxy)phenylamine B 14 l '-[(2S)-2-P-propyl]-5,6-dihydrospiro[benzo[1,2-7:5,4-b']dioxan-3,3'-^丨哚] -2·(ΓΗ)-_ A 14.1 l'-[(2S)-2-(indolyl)propyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4- b'] Dipyran-3,3'-p?| 嗓]·2'(1Ή)-keto B 14.2 r-{(2S)-2-[(4-fluorobenzyl)oxy]propyl 5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran_3,3,_吲哚]-2'(1Ή)-one B 14.3 l'-[( 2S)-2-〇*pyridin-2-ylmethoxy)propyl]_5,6-dihydrospiro[benzo[l,2-b:5,4?']difuran-3,3, -吲哚]-2,(1Ή)-keto B 14.4 Γ-(3-butyl-butyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran -3,3'-啕哚]-2'(1Ή)-ketone A 14.5 Γ-(4,4,4-trifluoro-3-hydroxybutyl)-5,6-dihydrospiro[benzo[l ,2-b : 5,4-b'] Furanyl _3,3,-叼丨哚]-2, (l,H)-g with B 15.1 Γ-{3-[(3-mercaptobutyl)amino]propyl b 5,6- Dihydrospiro[benzo[1,2-1>:5,47'] dis-melly-3,3'-吲哚]-2Χ1Ή)-ketohydrochloride B 15.2 1L{3-[butyl ( Methyl)amino]propyl propyl 5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3,-啕哚]-2, (1Ή) - ketohydrochloride B 15.3 Γ-{3-[(2,2,2-trifluoroethyl)amino]propyl b 5,6-dihydrospiro[benzo[l,2-b: 5, 4,7,]difuran-3,3,-吲哚]-2·(1Ή)-ketohydrochloride B 15.4 3-{[3-(2·-keto-5,6-dihydrospiro[benzene And [l,2-b: 5,4-b,] difuran-3,3W丨哚]-Γ(2Ή)-yl)propyl]amino}propionitrile hydrochloride B 143924-sp-20091127- 6 •1104· (8) 201020257 ❿ ❷ Example No. Compound name CYP3A4 % inhibition 16 4'-[6-(diamidoamine) acridine! Base]_r_[(2R)_tetrahydrofuran-2-ylmethyl]-5,6·dihydrospiro[benzo[1,2-7:5,4-b']difuran_3,3'-啕哚]-2'(1Ή)-ketooxime 16.1 4'-[(Ε)-2-(4-fluorophenyl)vinyl]·r_[(2R)_tetrahydrofuran-2-ylmethyl]-5,6 -Dihydrospiro[benzo[i,2-b : 5,4-b']difuran-3,3'-吲哚]-2,(1,11)-one oxime 16.2 4'-dibenzo [b,dM phen-4-yl-i, _[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzene^calling seven:5,4-7,]dipyran-3 , 3'-啕哚]-2, (γη)-ketooxime 16.3 4Η1-benzopyrimidine))_r_[(2R)_ra氲furan-2-ylindenyl]-5,6-dihydrospiro[ stupid And [ub: 5,4-b]difuran-3,3'-吲哚]-2,(1Ή)-ketooxime 16.4 4'-(1-methyl-1Η-吲哚-5-yl)- l,-[(2R)-Tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo(10)7:5,4-b,]didentate-3,3,5丨哚]- 2,(1Ή)-ketooxime 16.5 4'-[3,5-bis(tri-methyl)phenyl]_r_[(2R)_tetrahydrofuran-2-ylindenyl]-5,6-di-argon-[ Benzene [i,2-b : 5,4-b,] dipyran-3,3'-吲嗓]·2'(1Ή)-ketooxime 16.6 4'_(4-phenoxyphenyl H, -[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[^7:5,4?|]difur -3,3'-吲哚]-2'(1Ή)-ketone A 16.7 4'_[4_(2-methylpropoxy)phenyl]-1,-[(2R)-tetrahydrofuran-2-yl Indenyl]_5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3'-indole]-2,(1Ή)-one A 16.8 4' -(4-butoxyphenyl H,-[(2R)-tetrahydrofuran-2-ylmethyl]~5,6-dihydrospiro[benzo[1,2-b : 5,4-b,] Difuran_3,3'-吲哚]_2'(ΓΗ)-ketone A 16.9 4Κ4-formylphenyl)_r_[(2R)_tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[ Benzo[ub:5,4-b,]difuran-3,吲哚]-2'(ΓΗ)_ ketone oxime 16.10 4H5-yl-l,-[(2R)-tetrahydrofuran-2-ylmethyl] -5,6-dihydrospiro[benzo[ub:5,4-b']difuran-3,3·-吲哚]-2ΧΓΗ)-one oxime 143924-sp-20091127-6 -1105 - 201020257

Example No. Compound name % inhibition of CYP3A4 16.11 446-(diamidoamino)acridin-3-yl]-indole-{[5-(trifluoromethyl)furan-2-yl]indenyl}-5,6 -Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-吲哚]-2,(1Ή)-keto B 16.12 Γ-[(5-gas group 2-portophenenyl)methyl]-4·-[6-(dimethylamino)pyridin-3-yl]spiro[pyrano[2,3-f][l,3]benzoic Oxygen olefin-7,3'-啕哚]-2'(1Ή)-keto B 16.13 gas-based-2-»»secenyl)methyl]-4'-(3-bitjing) snail [blowing喃[2,3-f][l,3]benzodioxanthene-7,3·-吲哚]-2'(1Ή)-keto B 16.14 4'-[6-(dimethylamine Base>pyridin-3-yl]spiro[吱,[2,3-f][1,3]benzodioxene-7,吲哚]-2'(1Ή)-one B 16.15 Γ-Methyl-4'-(2-keto-2Η-nonene-7-yl)-2,3-dihydrospiro[pufrano[2,3-g][l,4]benzo Dioxogene-8,3'-啕哚]-2'(1Ή)-keto B 16.16 1'-Methyl-4'-(2-ketotetrahydropyrrol-1-yl)-2,3 - Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-oxime)-one A 16.17 1_methyl-4' -Mufu 1»林-4-yl-2,3-diaza snail [ρ夫0南和[2,3-g][l,4]benzoic Terpene-8,3'-啕哚]-2Χ1Ή)-ketone A 16.18 Γ-fluorenyl winter (2-ketopyridine-1(2H)-yl)-2,3-dihydrospiro[吱[2,3-g][l,4]benzodioxanthene_8,3'-吲哚]-2'(1Ή)-ketone A 16.19 4·-Amino-indole-indenyl-2 ,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8,34丨哚]-2'(1Ή)-ketone A 16.20 Ν-(Γ -Methyl-2'-keto-1',2,3-trihydrospiro[,,[2,3-g][l,4]benzodioxanthene-8,3' -吲哚]-4·-yl)cyclobutane carboxamide A 16.21 Ν-(Γ-methyl-keto-oxime, 2,2',3-tetrahydrospiro[吱,[2, 3-g][l,4]benzodioxanthene-8,3'-吲哚]-4'-yl)-2-(trifluoromethyl)benzamide A 143924-sp-20091127 -6 •1106- 201020257

Example No. two --------- Compound name ^ΥΡ3Α4^Γ % inhibition 16.22 N-(l,-methyl_2'-keto-oxime, 2,2,,3-tetrahydrospiro[唉喃[2,3-g][l,4]benzodioxanthene _8,3'-ρ5 pulo]-4'-yl)methanesulfonamide A 16.23 Ν-(Γ-曱 base -2·-keto-anthracene, 2,2',3-tetrahydrospiro [bite and - [2,3][1,4]benzodioxanthene-8,3,-吲哚]-4,·yl)cyclohexanecarboxamide A 16.24 Ν-(Γ-methyl-2'-keto-1',2,2',3-tetrahydrospiro[唉唉-~ [2 , 3-dan][1,4]benzodioxanthene-8,3,-4bido]-4'-yl)cyclopentanecarboxamide-------- A 16.25 Ν -(Γ-Methyl-2'-branched|yl-1',2,2',3-tetrahydrospiro[?,[2,3-g][l,4]benzodioxan Alkene-8,3·-吲哚]-4·-yl)acetamide ~~~——--- A 16.26 Ν-(Γ-曱-yl-2'-keto-1·, 2,2· ,3-tetrahydrospiro-cyano-[2,3-g][l,4]benzodioxanthene _8,3,-沔卜朵]·4,_yl)cyclopropanecarboxamide A 16.27 Ν-(Γ-Methyl-2·-keto-1',2,2',3-tetrahydrospiro [smeg front [2,3^][1,4] benzodioxanthine Alkenyl-8,3'-啕哚]-41-yl)benzamide------ B 16 .28 2-methoxy-indole-(Γ-methyl-2,-keto-1,2,2,3-trihydrospiro[吱,[2,3-g][l,4 Benzodioxanthene _8,3,_ 哚 哚]-heart group) acetamamine - A 16.29 Ν-(Γ-methyl-2'-keto-1', 2, 2', 3-tetrahydrospich. Nanhe [2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-4'-yl)propanamide A 16.30 Ν -(Γ-fluorenyl-2·-keto-oxime, 2, fluorene, 3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8, 3^ 哚]-4·-yl) pentamidine A 16.31 2,2-dimethyl-N-(l,-mercapto-2'-keto-1,2,2,3-trihydrogen Snail [吱,[2,3-g][l,4]benzodioxanthene-8,3^5丨嗓]-4'-yl) propylamine A 16.32 Ν-(Γ-甲Keto-2, keto-anthracene, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4] stupid and dioxane 圜-8,3,-啕哚]-4,-yl) hexamidine----------- A ------- 143924-sp-20091127-6 -1107- 201020257

Example No. Compound name CYP3A4 % inhibition 16.33 Ν-(Γ-Methyl-2'-keto-oxime, 2,2',3-tetrahydrospiro [p-fol-[2,3-g][l, 4] stupid and dioxane terpene _8,3'_呻哚]-4'-yl)heptanylamine B 16.34 2-(2-decyloxyethoxy)-fluorene-(1·-fluorenyl) -2'-keto-l',2,2',3-tetrahydrospiro[唉,[2,3-g][l,4]benzodioxene-8,3M丨哚] -4'-yl) acetamamine A 16.35 1-hexyl-3-(anthracene-fluorenyl-2'-keto-oxime, 2,2',3-tetrahydrospiro [bite-and-[2,3- g][l,4]benzodioxanthene _8,3'-吲哚]-4'-yl) pulse B 16.36 1-cyclopentyl-3-(anthracene-methyl-2·-one Base-Γ, 2,2',3-tetra-argon snail [bito-and-[2,3-g][l,4]benzodioxanthene_8,3,_吲哚]-4'- Urea A 16.37 1-cyclohexyl-3-(anthracene-methyl-2·-keto-1,2,2,3-trihydrospiro[吱,[2,3-g][l , 4] benzodioxanthene _8,3'-throindole]-4'-yl)urea A 16.38 1^-cyclohexyl-1'-methyl-2|-keto-1',2 , 2',3-tetrahydrospiro [bito-and-[2,3-g][l,4]benzodioxolene _8,3^ 哚]-4'-carboxamide A 16.39 N -cyclopentyl-indole-methyl-2'-yl-indole, 2,2\3-tetrahydrospiro[吱,[2,3-g ][l,4]benzodioxanthene·8,3Μ|哚]-4'-carboxyguanamine A 16.41 1·-mercapto-4'-(tetrahydron-p-indol-1-yl) -2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3'_吲哚]-2·(1Ή)-ketone A 16.42 Γ-Methyl-2'-keto-oxime-pentyl-1',2,2',3-tetrahydrospiro[吱〇南和[2,3-g][l,4]benzoic Oxadecene-8,3'-吲哚M'-carboxamide A 16.43 N-(2-methoxyethyl)-indole-methyl-2'-keto-i',2,2' , 3-tetrahydrospiro [bito-and-[2,3-g][l,4]benzodioxolene-8,3,5丨哚]-4'-carboxamide A 16.44 N-( 4-fluorobenzyl)-fluorenyl-methyl-2'-keto-1,2,2,3-tetrahydroindole [pyrano[2,3-g][l,4]benzoic Oxygen olefin-8, 义丨哚丨哚]-4'-carboxamide 143924-sp-20091127-6 -1108- 201020257

Example No. Compound name CYP3A4 % inhibition 16.45 N-hexyl-oxime-methyl-2·-keto-oxime, 2,2',3-tetrahydrospiro [, s-[2,3-g][l, 4] benzodioxanthene-8,3'-吲哚]-4'-carboxamide oxime 16.46 Γ-methyl-2'-keto-N-0pyridin-2-ylindenyl) -1',2,2·,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanene-8,3'-吲哚]-4'- Indoleamine A 16.47 N-(4-fluorophenyl)-indole-methyl-2·-keto-1',2,2',3-tetrahydrospiro[吱,[2,3-g] [l,4]benzodioxanthene-8,3·-丨嗓]-4'-retinamide A 16.50 4'-amino-1'-{[3-(trifluoromethyl)p Bis-2-yl]methyl}-2,3-dihydrospich-[2,3-g][l,4] benzodioxanthene-8,3·-啕哚] -2'(1Ή)-ketone A 16.51 4'-Hydroxy-2,3-dihydrospiro [biting and p,3-g][l,4]benzodioxanthene-8,3·-呻哚]-2·(1Ή)-ketone A 16.52 4'-hydroxy-indole-methyl-2,3-dihydrospiro[, succinyl[2,3-g][l,4] benzodioxole Lunene-8,3'-啕哚]-2'(1Ή)-ketone A 16.53 Γ-methyl-4·-(acridin-2-yloxy)-2,3-dihydrospiro[吱喃[2,3-g][l,4]benzodioxanthene-8,3'-thirsty]-2'(1Ή)-one B 16.54 4'-[2-(2-Methoxyethoxy)ethoxy]-Γ·methyl-2,3_dihydrospiro[吱,[2,3-g][l,4]benzene Dioxetine-8,3 Wh]-2Χ1Ή)-ketone A 16.55 Γ-fluorenyl-4'-{[3-(trifluoromethyl)p-pyridin-2-yl]oxy}- 2,3-Dihydrospiro|> Furano[2,3-g][l,4]benzodioxanene-8,吲哚]-2'(ΓΗ)-keto B 16.56 1' -methyl-444-(trifluoromethyl)phenoxy]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxol-8, 3'-吲哚]-2·(1Ή)-keto B 16.57 4'-(oxy)-indenyl-indenyl-2,3-dihydrospiro [bito-and-[2,3-g] [1 , 4] benzodioxanthene-8,3·-吲哚]-2'(1Ή)-ketone B 143924-sp-20091127-6 -1109- 201020257

Example number Compound name CYP3A4 % inhibition 16.58 Γ-methyl-4'-{[3-(trifluoromethyl), pyridin-2-yl] methoxy b 2,3-dihydro snail [taste and [2,3-g][l,4]benzodioxanthene-8,3^5丨嗓]-2,(ιή)-ketooxime 16.59 4'-(6-(didecylamine)比 _ 3 3 _ _ 七 七 七 _ _ _ _ _ _ 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨Luyuan _8,3'_ dihydroindole 1-2,-ketooxime 16.60 4'-(4-methoxy^pyridin-2-ylmethyl)_3,7-dihydro-2H-snail [Stupid and furan [5,6 seven like, 4] dioxetene-8,3'-dihydroanthracene] 嗣Β 16.61 (7S): 4'_ sniffer-3-yl-1'- Methyl snail [吱,[2,3_η[13] benzodioxene-7,3,-吲哚]-2'(1 Ή)-ketooxime 16.62 (7R)j'_biting- 3-yl-indole-methyl snail [吱,[2,3 rhyme] benzodioxol-7,3·-吲哚]-2,(1Ή)-ketooxime 16.63 (10):4' -Moji-1'-methylspiro- s-mercapto[2 3 f][13]benzodioxanthene -7,3'-β pudol]-2,(1Ή)-ketooxime 16.64 ( 7S)-4Hl'_曱基螺卜失η南和[2,3_叩,3]benzodioxolene-7,3,-啕哚]-2,(1Ή)-ketooxime 16.65 ( 7S)-4'_吱吱-3-yl snail [吱And [2,3_fp,3]benzodioxol-7,3'-啕哚]-2,(1Ή)-_ Β 16.66 (7R)-4L furanyl snail [biting cum [2, 3-f][l,3]benzodioxol-7,3,-吲哚]-2,(1Ή)-ketooxime 16.67 Γ-mercapto-4Η1Η-pyrazole winter base)_2,3 _ Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8 3,_吲哚2,(m)-嗣J Β 16.68 4′′fuan-3 -yl-indole-indenyl 2,3_dihydrospiro[,,[2,3-g][l,4]benzodioxene _8 3, 吲„ Β 16.69 a _4_ Base>2,3_Dichlorospiro[Bite °Nand[2'3-g][l,4] Benzodioxene _8 3,啕哚]_ 2'(ΓΗ)-网&quot ; ' —— A 143924-sp-20091127-6 •1110· 201020257

Example No. Compound name CYP3A4 % inhibition 16.70 Γ-methyl-4'-(l-methyl-lH-p than quaternary-4-yl)-2,3-dihydrospiro [furo[2,3-g ][l,4]benzodioxanthene 浠8,3,_ old 哚]-2Χ1Ή)-ketone A 16.71 Γ-methyl-2'--yl-1·,2,2\3 hydrogen Snail [吱,[2,3-g][l,4]benzodioxanthene_8,3,_吲哚]_4,_carbonitrile A 16.73 Γ-methyl-4·-(four Hydrogen pufran-3-yl) snail [cough sputum [2,3-f] [1,3] benzodioxos-7,3·- 巧丨嗓]-2·(1Ή) -keto B 16.74 Γ-methyl·4'-(5-methyl-1,2,4-β-di-salt-3-yl)-2,3-dihydrospiro[, s-[2,3- g][l,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-ketone A 16.75 4'-(3,5-Dimethylisoxazole) Heptamethyl_2 3_dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2 丨(1Ή)-one B 16.77 N-cyclobutyl-1·-methyl-2'-keto-l',2,2,3-trihydrospiro[snolo[2,3^][1,4]benzo Dioxetene _8,3,-throindole]-4'-carboxamide A 16.78 N,N,1-dimethyl-2·-yl-indole, 2,2',3-tetrachloro Snail [biting and [2,3-g][l,4] benzodioxanthene _8,3, -u5| 哚]-4'-carboxycarbamine A 16.79 4 -(3-methoxyphenoxymethyl-2,3_dihydrospiro[p-mono-[2,3-g][l, 4] benzodioxanthene _8,3,-蚓哚]-2'(ΓΗ)-ketone B 16.80 Γ-methyl-4-phenoxy-2,3-dihydro snail [cough mer [2,3-g] [1,4]benzodioxanthene-8,3'-〇?Budu]-2·(1Ή)-keto B 16.81 1'-Methyl-4'-( 3-morpholine-4-ylphenoxy)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'- ^Ι ^ ]-2'(1Ή)-^ B 16.82 4'-[(^.Methoxypyridin-3-yl)oxy]methyl_2,3_dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene-8,3'-mouth 哚]-2'(1Ή)-嗣A 143924-sp-20091127-6 -1111- 201020257 snail [taste ° Nanhe [3,2-e][2,l,3]benzoxanthene-2,3'-m|p-dot]_2'(1Ή)-one; 6-chloro-anthracene-pyrene ratio咬-2-ylindenyl)-2,3-dihydrospiro[吱,[3,2_f][i,4]benzodioxanthene-9,3'-W,]_2f(rH) , Γ7 淀 -2--2-yl fluorenyl) 2,3-dihydrospiro[吱,[3,2414]benzodioxanthene-9,3'-吲哚]-2' (1Ή )-ketone; 9-fluoro-l'-O-pyridin-2-ylindenyl)_2,3-diindole-spiro[ρ, 喃 并 [2,3_g][1,4]benzoic Oxalene-8,3·-啕哚]-2·(1Ή)-one; 9-failyl-Γ-{[3-(trifluoromethylididin-2-yl)methyl}·2 ,3-dihydrospiro[吱-and-β[2'3-g][l,4]benzodioxanthene,8,3'·delta]_2·(ι·η)_one; 9 -fluoro-indole-[(5-hydroxypyridin-2-yl)indolyl]_2,3-dihydrospiro[吱3[g][1,4] benzodioxanene-8, 3,-吲哚]-2,(1Ή)-one; 6-(5-methyl-1,2,4-oxadiazole_3_pyridin-2-oxazinyl) snail [μbenzo Furan-3,3'-啕哚]-2'(1Ή)-one; and 6-chloro-indenyl-{[3-(trifluoromethylcyclopyridine-2-yl)methyl}_2,3_ Dihydrospiro[吱,[3,2-f][l,4]benzodioxolene _9,3,-θ丨哚]-2'(1Ή)-one. Another embodiment of the invention is a compound of formula (V) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is a compound of formula (V) selected from the group consisting of: 1·-(diphenylmethyl)-3,4-dihydro-2Η-spiro!&gt ; 喃 并 [2,3-h][l,5]benzodioxanthene-9,3'-吲哚]-2'(ΓΗ)-one; 3,4-dihydro-2Η -Spirulina [furo[2,3-h][l,5]benzodioxaerythritol-9,3,-吲哚]-2 丫1Ή)-one; 1'-{[5-( Trifluoromethyl) acenaphthyl-2-yl] sulfhydryl 3,4-dihydro-2H-spiro[吱,[2,3-h] 143924-SP-20091127-1 •113- 201020257 ----- The % inhibition of the compound name CYP3A4 is 16.83 4'-(1,3-dihydro-oxo-5-yloxymethyl-2,3-dihydrospiro[pf" Nanhe [ 2,3-g][l,4] benzodioxanthene-8,3'-吲哚]-2·(1Ή)-ketooxime 16.84 4Η4-methoxyphenoxy)-1'_ Mercapto-2,3_dihydro^[2,3-g][l,4]benzodioxanthene_8 3, 丨哚]-2'(1Ή)-ketooxime 16.85 曱Base_4 decapyridin-2-ylmethoxy)_2,3_dihydropyrano[2,3-g][l,4]benzodioxanthene_8 3,丨哚]-2 '(ΓΗ)-ketooxime Β 16.86 1'-mercapto-4-(4-fluorobenzyloxy) 2,3_dihydrospiro-[10,3$][1'4]benzene And dioxerelate _8,3, 哚16.87 4-(4-fluorophenoxy) stilbene 2,3_dihydrospiro f [2'3-g][l,4]benzene Dioxetemene _8 3,_吲哚2'(l'H)-ig Β 16.88 1 phenyl)methyl]士(6-methoxy 峨-3-yl) snail [1-本And furan _3,3, _10] 2,(1Ή)_ketooxime 17 1 -(4-hydroxyindolyl)5,6-dihydrospiro[benzo[u_b:mm-furan-3,3 '-吲哚]_2,(1'HV 嗣Β 17.1 i -(4^^卞氢螺[2 3_幻[14] 本一一氧氧圜-8,3,-吲哚]_2,(1Ή)-ketooxime 17.2 18 18.1 1 propyl" digastric snail [吱味和[^纽1,4] 并一乳地园-8,3,-吲哚]-2,( 1Ή)-ketone ____-—— A 2 \基^2 snail [1吱 并[2,3.,4]benzodioxolene-8,3 -吲哚]-Γ(2Ή) -Carboxylic acid ethyl ester 4_1 & base ring 2 anaerobic 7?, [, ° Nanhe [2,3.,3] benzodioxane A ____——---- Β ^ A __ 18.2 2-嗣 diyl Oxygen 2 terracotta [1,4] benzo: U 琊 · 8,3 - 吲哚Η, (2 Ή) _ carboxylic acid third _ J ——---- --- 143924-sp-2009i 127- 6 -1112- (S) 201020257

Example No. Compound name CYP3A4 % inhibition 19 l'-{[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-tetramethyltetrahydro-3aH-bis[1,3]dioxo圜 并 [4,5-b : 4·,5·-(1]piperid-5-yl]indolyl}-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene-8,3'-呻哚]-2·(1Ή)-ketone A 20 6-deoxy-6-(2'-keto-2,3-dihydrol Snail [吱,[2,3-g] [1,4]benzodioxanthene-8,3'-啕哚]-Γ(2Ή)-yl)-D-half-milk 21 Γ-cyclopropyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-2·( ΓΗ)-ketone A 22 Γ-acetamido-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8,3·-<哚]-2·(1Ή)-ketone A 23 Γ-{[4-(trifluoromethyl)>pyridin-2-yl]methyl}-2,3-dihydrospiro [bite-and-[2, 3-g][l,4]benzodioxanthene-8,3'-叼h]ketone A 24 41-ethenyl-indole-methyl-2,3-dihydrospiro[furan [2,3-g] [1,4]benzodioxanthene-&31-吲哚]-2'(1Ή)-ketone A 25 Γ-mercapto-4·-(2-methyl -1,3-Oxazol-4-yl)-2,3-dioxaspiro[吱,[2,3-g][l,4]benzodioxolene-8,3·-吲哚]-2 (ΓΗ)-keto B 26 4Η2-amino-1,3-pyrazol-4-yl)-indole-methyl-2,3-dihydrospiro[,,[2,3-g][l, 4] benzodioxanthene-8,3·-吲哚]-2'(1Ή)-one B 27 4'-(5-hydroxy-1Η-pyrazol-3-yl)-1,-曱Base-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3·_吲哚]-2'(1Ή)-ketone A 28 Γ-[3-(3-Mercapto-1,2,4′′diazol-5-yl)benzyl]-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene _8,3'-吲哚]-2'(1Ή)-ketone A 29.1 144-(3-Amino-1Η-pyrazol-5-yl)]]-3 -methylspiro[吱,[3,2-f][l,2] benzisoxazole-5,3,-啕哚]-2'(1Ή)-keto hydrochloride B 143924-sp- 20091127-6 -1113- 201020257

Example No. Compound name CYP3A4 - % inhibition 29.2 Γ-[4-(3-Amino-1H-pyrazol-5-yl)-yl]-2,3-dihydrospiro[吱,[2,3- g][l,4]benzodioxanthene_8,3'_啕哚]-2'(1Ή)-ketohydrochloride Β 30 Γ-[4-(3-methyl-1,2 , 4-oxadiazol-5-yl)-yl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene _8,3丨_ Rugged]-2,(1Ή)-ketone A 31 2·-keto-oxime-(pyridin-2-ylmethyl)-1·,2,2,3-trihydrospiro[furan[2] ,3-g][l,4]benzodioxanthene_8,3,-吲哚>5'-carboxamide A 32 14(6-norfosolin-4-ylpyridine-3- Methyl]-2,3-dihydrospiro[?,[2,3-g][l,4]benzodioxanthene-8J-吲哚]-2'(1Ή)-one Β 32.1 1'-{[6-(dimethylaminoidin-3-yl)methyl b 2,3_dihydrospiro[吱,[2,3-g][l,4]benzoic Oxygen ore _8,3'-吲哚]-2'(1Ή)-ketone A 32.2 1'-{[6-(diammonium)>pyridin-2-yl]methyl b 2,3 - Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-叼丨哚]-2'(1Ή)-ketooxime 33.2 5,6 -difluoro-r-{4-[(3R)-tetrahydropyrrol-3-ylamino] yl} snail [1- benzofuran-3,3 -吲哚]-2'(1Ή)-ketohydrochloride Β 33.3 1 _[(5-?福Ρ林~4-基ρ比乙-yl)methyl]-2,3-dihydrospiro [吱吱[2,3-g][l,4]benzodioxanthene_8,3'-吲哚]-2Χ1Ή)-ketone A 33.4 1'-{[5-(dimethylamine Acridine-2-yl]methyl}-2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-port哚]]-2'(1Ή)-嗣Β 34 1 -[(6-Aminopyridin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene _8,3,-< 哚]-2'(1Ή)-ketooxime 35 1 -[(6-keto-1,6-dihydropyridine-3- Methyl]_2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxane! 4 ocene-8,3'-吲哚]_2'(1Ή) -ketone A 143924-sp-20091127-6 -1114-

201020257

Example No. Compound name CYP3A4 % inhibition 35.1 Γ-[(2-hydroxypyrimidin-5-yl)methyl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzene And dioxerelmene _8,3,5丨哚]-2'(1Ή> ketone A 36 1·-[(1-methyl-6-keto-1,6-dihydroρ ratio bite_3 ·Methyl]-2,3-dihydrospiro[?,[2,3-g][l,4]benzodioxolene-8,3M丨哚]-2'(1Ή) -ketone A 37 Γ-[(6-amino ρ than -3-yl) fluorenyl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzoic氡陆园烯_8,3·-吲哚]-2'(1Ή)-ketone A 38 Ν'-hydroxy-Ν-{5-[(2·-keto-2,3-dihydrospiro[吱喃,P,3-g][l,4]benzodioxanthene _8,3·- pp-dot]-Γ(2Ή)-yl) fluorenyl]p than bite-2-yl} Iminocarbamamine A 39 Γ-([1,2,4]triazolo[l,5-a]pyridin-6-ylmethyl)-2,3-dihydrospiro[吱喃[2 ,3-g][l,4]benzodioxanthene-8,3. 哚]-2'(1Ή)-keto B 41 6-[(2·-keto-2,3-di Hydrorungac-[2,3-g][l,4]benzodioxolene-8,3'-啕哚]-1·(2Ή)-yl)methyl]pyridine-2-yl Nitrile A 42 6-[(Τ-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan) -8,3'-吲哚]-Γ(2Ή)-yl)methyl]pyridin-2-carboxyguanamine B 44 3-amino-indole-(4-decyloxybenzyl) snail [3,2_幻[1,2]Benzene 11" sits -5,3'->15 Bulai]-2'(1'11)-keto B 44.1 3-Amino-Γ-( Acridine·2-ylmethyl) snail [c- ace[3,2_η[1,2]benzoindole-5,3'-(f)嗓]-2'(1Ή)-ketone A 44.2 3-amine -l'-[(2R)-izghydroindol-2-ylindenyl]spiro[pf-pyrano[3,2-f][l,2]benzisoxazole-5,3'-啕哚]-2·(1Ή)-ketone A 44.3 3-Amino-indole-[2-(trifluoromethyl)-yl] snail [Miso-[3,2-f][l,2]benzene And isoxazole-5,3|-吲哚]-2'(lΉ)-ketone B 143924-sp-20091127-6 -1115- 201020257

Example number Compound name % inhibition of CYP3A4 45 6-carbyl-2'-keto-l'-[(2R)-izg hydrogen rousing-2-ylmethyl]_ Γ, 2'-dihydrospiro[1 -benzofuran-3,3'-thoracic acid]-5-carbonitrile A 45.1 6-hydroxy-2'-keto-l'-[2-(trifluoromethyl)] group], Γ, 2, _ Dihydrospiro[1-benzofuran-3,3'-啕哚]-5-indolecarbonitrile A 46 1·-[2-(trifluoromethyl)benzyl]-1Η-spiro[吱喃[3 ,2-f]carbazole-5,3'-啕哚]-2'(1Ή)-keto B 46.1 Γ-(acridin-2-ylmethyl)-1Η-snail [吱喃[3,2丨?-5,3'-port?1 嗓]-2,(ΓΗ)- Brewing I-A 46.2 Γ-((3-(Trifluoromethyl)ρ pyridine-2-yl) fluorenyl) ^心二氢螺[3,2-fHazole-5,3,-dihydroindole]-2.-one B. All the US patents cited in this patent specification, the United States The patent application bulletin, the four-country patents, the foreign patents, the foreign patents, and the non-patent publications are given in their entirety. Although the description of the invention has been generally detailed --, W ... training { from the fruit dam team for the month, but the changes and amendments can be included in the scope of the attached request = ̄ therefore the specific implementation The examples are to be considered as illustrative and not limiting, and the invention is not to be construed M3924-sp-2〇〇9l 127-6 -1116-201020257 t1,5] benzodioxine heptadecene-9,3'-呻哚]-2'(1Ή)-one; Γ-(10)唆- 2-ylindenyl)_3,4_dihydro-2Η·spiro[吱,[2,3_h][1,5]benzodiazepines-decene-9,3,-吲哚]-ΜΓΗ) -ketone; 1'-[(211)-tetrahydrofuran-2-ylmethyl]_3,4-dihydro-2Η-spiro[吱,[2,3-7][1,5]benzodioxine-7 Terpene-9,3·-吲哚]-2,(1Ή)-one; l'-[(2R)-l,4-dioxoindole_2·ylindenyl]_3,4_dihydro- _ _ 螺 [吱 并 [2,3_h] [1,5] benzodiazepine heptarene _9,3, _ 吲哚]-2, (1 Ή)-ketone; or l'-[(2S )-l,4-dioxoland-2-ylindenyl]-3,4-dihydro-2-indole-spiro[吱,[2,3-h][1,5]benzodioxine-7 Terpene _9,3,_吲哚]_2, (1,H)-ketone. Another specific embodiment of the invention is a compound of formula (VI) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is a compound of formula (VI) wherein z is _〇_ or -N(H)-' and R1〇a is hydrogen or fluorenyl. In this particular embodiment, a specific embodiment is a compound of formula (VI) wherein z is 〇-, and R10a is fluorenyl. In this particular embodiment, a specific embodiment is a compound of formula (VI) wherein z is -N(H)- and RiQa is hydrogen. ❿ In this particular embodiment, a specific embodiment is a compound of formula (VI) selected from the group consisting of: 1'-[2-(trifluoroindolyl HH_ snail [吱,[3,2 咖丨Azole _5,3,(9)哚] ie ή) ketone; Γ-(10) gnato-2-ylmethyl)-1 Η-spiro [biting mers [3, carbazole _5 3, 吲哚]_2, ( ή)) ketone; r-((3-(tri-m-methyl)>-bit-2-yl)methyl hydrazine, 6_diox snail [biting β南和[3,2 Μ嗤143924-sp-20091127 -1 . 114 (S) 201020257 -5,3'-dihydroanthracene]_2'-one; 1L (4-decyloxybenzyl)methylspiro[吱,[3,2-f][ l,2]benzisoxazole-5,3,-吲哚]-2'(1Ή)-one; 3-methylspiro[吱,[3,2_f][i,2] benzisoindole Azole-5,3'-吲哚]-2'(ΓΗ)-one; 3-methyl-1'-{[5-(trifluoromethyl)pyran-2-yl]indenyl} snail喃[[Hungry]benzisoxazole-5,3·-啕哚]-2,(1Ή)-one; 3-methyl-oxime-(pyridine·2_ylindenyl) snail And [3,2<][1,2]benzisoxazole_5,3,_ 呻哚]-2·(1Ή)-_ ; ® 3-methyl-1·-(pyridin-3-yl) Scorpion) snail [吱,[3,2-f][l,2] benzisoxazole_5,3,-吲哚]-2Χ1Ή)-one; 3-methyl-14 (2 feet) -tetrahydrofuran-2-ylmethyl] snail [bite And [3,2-f][l,2] benzoisoxazole-5,3'-吲哚]-2,(1Ή)-one; Γ-(4-isoxazol-5-ylbenzyl -3-mercaptospiro[吱,[3,2-f][l,2]benzisoxazole-5,3'-啕哚]-2,(1Ή)-one; 3-methyl -1·-[2-(trifluoromethyl)-yl;|spib-m-[from 叩2] benzisoxazole-5,3'-^Ι ^]-2'(1Ή)-^ ; ❿ 3-methyl-r-{[3-(trifluoromethyl)acridin-2-yl]methyl μ tired [吱,[3,2412] benzoisozaki °-5,3Ί嗓]-2'(1Ή)-ketone; 1'-[2-(2-methoxyethoxy)ethyl]_3_indolyl snail [吱然[[幻(1)幻苯苯异°°°坐-5,3'-吲嗦]-2'(1Ή)-鲷; 3-methyl-indole-(3-methylbutyl)spiro[吱2-[2 2-^^ 2] benzisoindole Azole _5 3•吲哚]-2 丫1Ή)-ketone; 3-methyl-indole-(pyroxy-2-ylmethyl) snail [吱-benzo-isoxazole _5,3,_ <;哚]-2'(1Ή)-ketone; 143924-SP-20091127-1 •115- 201020257 14(3-Fluoropyridin-2-yl)methyl]-3-methylspiro[furo[3, 2-f][l,2]benzisoxazole-5,3'-吲哚]-2'(1'11)-one; 2-[(3-indolyl-2'-oxo snail喃[3,2-f][l,2]benzisoxazole_5,3,_蜊哚]_ 1'(2Ή)-yl)methyl]-1,3-11 -4- oxoic acid ester; 2- [(3-mercapto-2'-oxaspiro[吱,[,,[,,,,,,,,,,,,,,,,,,,,,,,, »5丨嗓]- 1'(2Ή)-yl) fluorenyl]-1,3-yttrium-4-deoxy acid; Ν,Ν-dimercapto-2-[(3-methyl-21-oxygen) Snail [bito[3,2-f][l,2]benzisoxazole-5,3·-啕哚]-Γ(2Ή)-yl)indolyl]-1,3-indazole Carboxylamidine; 3-{4-[(3-mercapto-2'-oxaspiro[furo[3,2 rhythm 1,2] benzisoxazole_5,3,_峋馨51]]- Γ(2Ή)-yl)methyl]phenyl}_3_ketopropenyl nitrile; or Γ-[4-(3-amino-lH-p than 嗤-5-yl) fluorenyl] [吱吱[3,2-f][i,2]Benzoiso 1^°°Sit-5,3'-吲嗓]-2'(1Ή)-ketohydrochloride. In this particular embodiment, a specific embodiment is a compound of formula (VI) wherein Ri0a is -NH2. In this particular embodiment, a specific embodiment is a compound of formula (VI) selected from the group consisting of: 3-amino-indole-(4-methoxyindenyl) snail Carbazole _5,3,_ 〇吲哚]-2'(1Ή)-one; 3-amino-indole-(pyridin-2-ylindenyl) snail [唉][nau]benzoiso-β Azole-5,3,_峋哚]-2'(ΓΗ)-one; 3-amino-r-[(2R)-rahydrofuran-2-ylindenyl] snail [吱-benzo benzoindole] Azole-5,3^^ 哚]-2'(1Ή)-one; or 3-amino-indole-[2-(trifluoromethyl)-yl] snail [吱,[3,2_耶, 2] Benzoisoxazole-5,3'-β 哚]-2'(ΓΗ)-one. 143924-sp-20091127-l-116-(S) 201020257 A further embodiment of the invention is a compound of formula (VII) as set forth above in the Summary of the Invention. In this particular embodiment, the specific embodiment is a compound of formula (VII) wherein Y is -〇. In this particular embodiment, another embodiment is a compound of formula (VII) wherein ¥ is s_. In this particular embodiment, another embodiment is a compound of formula (10)) selected from the group consisting of: ® 2-mercaptospiro[吱,[2,3-η[ι,3]benzopyrene] 7,3,吲嗓]_2,(1Ή)嗣; Γ-(diphenylmethyl)-2-methylspiro[唉丁和[2 3413]benzoheptazole _7,3,吲哚2' (1Ή)-ketone; 2-methylspiro[吱,[2,3-f][l,3]benzo-salt-7,3.-4-disalone]-2,(1Ή)-class; 2-methyl-indole-(3-methylbutyl) snail [bito-benzo benzopyrazole _7,3,_啕哚]-2'(ΓΗ)-one; 2-methyl-[-( Tetrahydro-2Η-piperidin-4-ylmethyl) snail [glycino[2,3-f][i,3]benzopyrazole-7J-吲哚]-Τ(1Ή)-one; 2 -mercapto-l'-[(2R)-tetrahydrop-pentan-2-ylindenyl]spiro[吱,[2,3-f][l,3]benzoxazole-7,3' -吲哚]-2'(1Ή)-ketone; 2-methyl-indole-(pyridin-2-ylmethyl) snail [bito-and-[2,3-f][l,3]benzopyrazole -7,3·-吲哚]-2'(1Ή)-one; or 14(5-chloro-1-indolyl-1Η-imidazol-2-yl)indolyl]-2-methylspiro[furan And [2,3-f][l,3]benzothiazole-7,3'-啕哚]-2·(1Ή)-one. Another embodiment of the invention is a compound of formula (VIII) as set forth above in the Summary of the Invention. 143924-sp-20091127-l - Π7- 201020257 In this particular embodiment, a specific embodiment is a compound of formula (VIII) wherein w is a direct bond. In this particular embodiment, a specific embodiment is a compound of formula (VIII) selected from the group consisting of: Γ-(diphenylfluorenyl)-1-indenyl snail [snolo[3,2-f][l ,3]benzo-3-oxazole_7 3,_ρ5丨嗓]_ 2,2'(1Η,1Ή)-dione; 1-mercaptospiro[furo[3,2-f][l,3] Benzooxazole-7,3·-吲哚]_2,2,σΗ,1Ή>·dione; or 1-methyl-1'-[(211)-tetrahydrobetic β-nan-2-ylmethyl Snail [ρ夫°南和[3,2-f][i,3]Benzene# _ azole-7,3'-吲哚]-2,2'(1Η,1Ή)-dione. In this particular embodiment, a specific embodiment is a compound of formula (VIII) wherein w is _CH2_. In this particular embodiment, a specific embodiment is a compound of the formula selected from the group consisting of: Γ-(diphenylmethylhydrazine-methyl-1Η-spiro[吱,[3,2-g][l,4 Benzoindolin m 哚]-2,2'(1Ή,3Η)-dione; 1-methyl-1Η-spiro[吱,[3,2-g][l,4]benzoan Plowing -8,3,-吲哚]-2,2'(1Ή,3Η)-❺ diketone; or 1-mercapto-14 (2 phantom-tetrahydrofuran-2-ylmethyl fluorene-snail [3,2_§][1,4]Benzene 11 tillage-8,3'-吲哚]-2,2,(1Ή,3Η)-dione. Another embodiment of the present invention is as above A compound of formula (IX) as set forth in the Summary of the Invention. In this particular embodiment, a specific embodiment is a compound of formula (IX) wherein U is directly bonded. -118- 143924-sp-20091127- 1 (S) 201020257 In this particular embodiment, a specific embodiment is a compound of formula (IX) selected from the group consisting of: Γ-(diphenylhydrazinyl)-3-indolyl snail [cough merging [2,3] -f][l,3]benzoxazole 3-mercapto-indole-dea-[2,3-f][l,3]benzo-4 "sitting -7,3,-吲嗓]-2 , 2,(1Ή,3Η)-dione; 3-mercapto-purine-{[5-(trifluoromethylidene ketone-2-yl) fluorenyl} snail [吱,[2,3_ 13] And carbazole-7,3'-吲哚]-2,2,(1 ugly, 311)-dione; or _ 3_methyl-1'-((())-tetrahydrofuran-2-yl) ))-2Η-spiro[benzofuro[6,5♦ oxazol-7,3,-dihydroanthracene-2,2,(3Η,6Η)-dione. In this particular embodiment A specific embodiment is a compound of formula (IX) wherein U is _Ch2_. In this particular embodiment, a specific embodiment is a compound of formula (IX) selected from the group consisting of: 4-methyl-4,7 - Dihydrospiro[benzofuro[5,6-7][1,4]哼耕-8,3'-dihydrou 哚]-2\3(2Η)-dione; or 4-methyl -l'-[(2R)-Eg hydrogen ρ 喃 -2--2-ylmethyl]-2 Η- snail [吱,[2,3-g][l,4]benzosin -8,3' -吲哚]-Τ, 3(1Ή,4Η)-dione. Another embodiment of the invention is a compound of formula (X) as set forth above in the Summary of the Invention, which is 1'-[( 2 feet)-tetrahydrogenate 〇South_2_ylmethyl]spiro[benzo[l,2-b:5,4-b']difuran-3,3'-呻哚]-2,,5 (1Ή,6Η)-Dione oxime Another embodiment of the invention is a compound of formula (XI) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is wherein versus γ Both 143924-sp-20091127-1 -119- 201020257 Each is a compound of formula (XI) of -CH2-. In this particular embodiment, a specific embodiment is a compound of formula (XI) selected from the group consisting of: K-diphenylmethyl^,^,-tetrahydrospiro(tetra)pyrene-^naphthyl------ ; 5',6',7',8'-tetrahydrospiro[峋嗓-3,3'-tea and [2,3-1)]isan]_2(111)-one; or 1-[( 2R)-tetramethane-2-ylmethyl]_5',6',7',8'-tetrahydrospiro 5丨嗓-3,3,-荇[2,3-b]biting ]-2(1H)-ketone. In this particular embodiment, a specific embodiment is a compound of formula (XI) wherein v is _〇_ and Y is -N(CH3)_. In this particular embodiment, a specific embodiment is a compound of the formula (χι) selected from the group consisting of: 1-indenyl-1'-{[5-(trifluoromethyl)anthracene-2-yl]fluorenyl }_2 3 dihydro-1 snail [吱,[3,2-g][l,4]benzoindole-8,3'-吲哚]_2'(ι,η)-keto hydrochloride; Or 1-methyl-l'-[(2R)-tetrahydrofuran-2-ylmethyl]_2,3-dihydro[bito-benzo-benzophenanthene]_2'(i'h)-ketohydrochloride salt. In this particular embodiment, a specific embodiment is a compound of formula (XI) wherein 乂 is 扣-) and Y is Ο-. In this particular embodiment, a specific embodiment is a compound of formula (XI) which is 4-methyl-1'-[(21^)_tetrahydrofuran-2-ylindenyl]3 4•dihydrogen _2H snail [biting and [2,3-g][l,4] benzo p-p well-8,3Ί 嗓]_2'(i,h)-ketone. In this particular embodiment, the specific embodiment is where v is -CH2. and γ is _〇_ (Deng compound. In this particular embodiment, a specific embodiment is a formula (χι ) compound, 143924-sp-2009l 127-1 -120- 201020257 selected from: 1 'seven ratio D-di-2-ylmethyl)-7,8-dihydro-6H-spiro-[唉喃[2, 3 Mickey _3,3, 哚]-2'(1Ή)-ketone; or Γ-{ [3-(trifluoromethyl)indol-2-yl]methyl b 7,8-dihydroanthracene _ snail [唉 并[2 3_g] decene-3,3'-吲哚]-2'(1Ή)-ketone. Another embodiment of the invention is a compound of formula (XII) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is a formula (χπ) compound Φ selected from the group consisting of: 6-mercapto-1 -(pyridin-2-ylindenyl)-2,3-dihydrospiro [ I,4-dioxaindole[2,3_η 啕哚-8,3'-吲哚]-2,,7(1Ή,6Η)-dione; or 6-methyl-2,3-di Hydrogen snail [1,4-dioxene ortho-[2,3_f]吲嗓_8 3,_啕嗓]_ 2V7(1'H,6H)-dione. Another embodiment of the invention is a compound of formula (XIII) as set forth above in the Summary of the Invention. In this particular embodiment, a specific embodiment is a compound of the formula (ΧΠΙ), selected from the group consisting of: Γ-(diphenylmethyl)-2,3,6,7-tetrahydrospiro[吱 并 and p , 2_g] 咣 _5,3,·啕哚]_ 2'(1Ή)-ketone; 1 -{[3-(difluoromethyl)ρ pyridine-2-yl]methyl b 7,8_ Dihydrospiro[dioxyterpene [2,3-g][l,3]benzodioxene _4,3, _10]_2,(1Ή) ketone; 2,3, 6,7-tetrahydrospiro[唉,[3,2-g]decene_5,3,_ten]_2,(1Ή)-one; or Γ-{[5-(trifluoromethyl Fu-2-n-yl]methyl}_2,3,6,7-tetrahydrospiro[吱,[3,2_g] octa--5,3'-吲哚]_2'(ΓΗ)-one. >..-- 143924-sp-20091127-l • 121 - 201020257 Another specific embodiment of the invention is a compound of formula (la):

Wherein: R15 is as follows for formula 1, formula (9), formula, formula (IV), formula (V), formula (VI), formula (VII), formula (VII), formula (vm), formula (ι) and Formula (χΙ) compounds are set forth above in the Summary of the Invention; R16 is as defined individually for R2, R4 or r6 in the compounds of Formula 1, Formula (9) and Formula (ΠΙ), as set forth above in the Summary of the Invention; Is a fused ring selected from the following:

Wherein J, K, L, M, U, V, W, Y and Z are as defined in relation to formula (I), formula (m), formula (VI), formula (VII), formula (VIII), formula (IX) , as described in the above formula (XI) and formula (ΧΙΙΙ), or as a single substituent on the phenyl ring (ie, not a fused ring), selected from _N(R26)R27 , _OR3〇 or -cxo)!^ 'The ruler' and the ruler 27 are each independently wind, burnt base, aryl group substituted as appropriate or replaced as appropriate 143924-sp-20091127-1 •122- 201020257 An aryl group; R30 is an alkyl group, a cycloalkyl group or a heterocyclic group, and R31 is a leukosyl group or a dentate group; a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically thereof An acceptable salt, solvate or prodrug. Another embodiment of the invention is a method of treating, preventing or ameliorating a disease or condition in a mammal, preferably a human, wherein the disease or symptom is selected From the following groups: pain, depression, cardiovascular disease, respiratory disease and psychiatric diseases and combinations thereof, and wherein the method includes breastfeeding as needed A therapeutically effective amount of a compound of the present invention as described above, which is a stereoisomer, a palmomer, a tautomeric complex or a mixture thereof, or a pharmaceutically acceptable salt or solvent thereof Or a prodrug, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention as described above, as a stereoisomer, a palmomer, a tautomer: a conformation or a mixture thereof, Or a pharmaceutically acceptable salt, solvate or pharmaceutically acceptable drug thereof, and a pharmaceutically acceptable excipient. The specific embodiment is a group wherein the disease or symptom is selected from the group consisting of Group: neuropathic pain, inflammatory pain, visceral pain, cancer pain, chemotherapy pain, injury pain, surgical pain, post-operative pain, production pain, labor pain, neurogenic bladder, cancerous colitis, Chronic pain, persistent pain, peripheral media ulcer, central media pain, chronic headache, migraine, sinus node headache, fantasy limb pain, peripheral nerve injury and their combination / specific ^ The other item is the group or the symptom is selected from the group consisting of: pain associated with Cong, Liao treatment institute 143924-SP-20091127-1 • 123- 201020257 caused by neuropathy, trigeminal neuralgia, Post-secret neuralgia, normal pain, heat sensitivity, local sarcoidosis, irritating bowel syndrome, Crohn's disease, pain associated with multiple sclerosis (MS) 'muscle atrophic lateral cord: ALS j diabetic patients with neuropathy, peripheral neuropathy, arthritis, rheumatoid arthritis, osteoarthritis, atherosclerosis, paroxysmal dystonia, muscle weakness, Cai, myotonia, malignant hyperthermia, gallbladder fibrosis, pseudo-acid Hyperketosis, striated muscle turnover, hypothyroidism, bipolar inhibition, anxiety, schizophrenia, nanochannel toxin-related diseases' familial acral red pain, primary acral red pain, familial rectal pain , cancer, tumor pain, partial and general tension, restless foot syndrome, irregular rhythm, fibromyalgia, neuroprotection in the state of blood stasis caused by stroke or nerve damage, fast festival Arrhythmia, atrial fibrillation and ventricular fibrillation. Another embodiment of the present invention is a method for treating pain in a mammal, preferably a human, by inhibiting ion flux through a voltage-dependent sodium channel in the mammal, in which the method includes A desirable embodiment of a compound of the present invention as described above is a stereoisomer, a palmomer, a tautomer or a mixture thereof or a pharmaceutically acceptable salt thereof, A solvate or prodrug, or a pharmaceutical composition '纟 comprises a therapeutically effective amount of a compound of the invention as described above' as: an isomer, a palmomer, a tautomer or a mixture thereof A pharmaceutically acceptable salt, solvate or prodrug thereof, and a pharmaceutically acceptable excipient. Another embodiment of the present invention is a method for treating or preventing hypercholesterolemia in a mammal, preferably a human, "This method includes 143924-sp-20〇91127-l 201020257. A mammal is administered a therapeutically effective amount of a compound of the invention as described above, as a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt thereof, a solvate or a medicinal composition, or a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention as described above, as a stereoisomer, a palmomer, a tautomer or a mixture thereof, or A pharmaceutically acceptable salt, solvate or prodrug' and a pharmaceutically acceptable excipient. A further embodiment is a method of stimulating benign prostatic hyperplasia in a mammal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of the invention as described above 2 Specific examples of the compound 'is a stereoisomer, a palmo isomer, a mutual: a mixture thereof' or a pharmaceutically acceptable salt, solvate or precursor thereof, or a pharmaceutical compound And a pharmaceutically acceptable salt or solvate thereof, wherein the compound of the invention is as described above, in the form of a therapeutically effective amount of the compound of the invention, a stereoisomer, a palmo isomer, a substance: ΐ::: a mixture thereof Or a precursor music' and a pharmaceutically acceptable excipient. The other embodiment of the present invention is a method for treating or preventing astringent pain in a mammal, preferably a human, wherein the method comprises administering a therapeutically effective amount to a milk animal: The above-mentioned compound of the present invention is: 'is a stereoisomer, a palmomer, a tautomer or a pharmaceutically acceptable salt, solvate or prodrug X thereof or a pharmaceutical composition, The invention comprises a therapeutically effective amount of a compound of the invention as described above, which is preferably a magnetic material or a mixture thereof, wherein the ratio is the same as that of the upper palm isomer, the tautomerization, and the bismuth. , solvate or precursor 143924-sp-20091127-1 -125- 201020257 a drug, and a pharmaceutically acceptable excipient. Another embodiment of the invention is a method of treating or preventing cancer in a mammal, preferably a human, wherein the method comprises administering to a mammal in need thereof a therapeutically effective amount of a compound of the invention as described above. And a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, or a pharmaceutical composition thereof, A therapeutically effective amount of the present invention as described above: month: compound 'is a stereoisomer, a palmomer, a tautomer or a mixture thereof, or a potent drug A salt, solvate or prodrug, and a pharmaceutically acceptable excipient are added. The present invention is specifically directed to a method of reducing ion flux through a dust-dependent sodium channel in a mammalian cell, which comprises reacting a cell with a compound of the invention as described above: a stereoisomer thereof, a palm Ligand, broadcast, 1 oxime, tautomers or mixtures thereof, or "acceptable salts, solvates or prodrugs." Specific embodiments of the compounds of the invention In the preparation of the present invention, the utilization and test of the compound of the present invention will be inhibited in mammals, preferably by inhibiting ion transport, especially in humans, and inhibiting ion flux through electromilling dependence. : 2: On the basis of partial or complete inhibition or prevention of ion flux, sometimes referred to as "blocking", and corresponding, text preparation,. A boat & Q von von blocker or "Suppressor", the compound of the present invention will modulate the sodium to inhibit the sodium channel's electrical dependence activity activity down, and / or reduce or prevent sodium ion pass 143924 -sp-20〇91127-1

-126- 201020257 The amount of cells across the cell membrane is prevented by sodium channel activity, such as ion flux. The compounds of the invention inhibit ion flux through voltage dependent sodium channels. These compounds are preferably sodium channel state or frequency dependent modifiers having low affinity for the resting/male closed state and high affinity for the inactivated state. These compounds may interact with overlapping locations in the lumen of the sodium-conducting pores of the channel, as described for other state-dependent nanochannel blockers (Cesme, s. et al.). These compounds may also interact with locations outside the lumen and have an ectopic effect on the passage of the steel pores through the channel pores. Any such result may ultimately be responsible for the overall therapeutic benefit provided by such compounds. Thus, the compounds of the invention are sodium channel blockers and are therefore useful in the treatment of diseases and conditions in mammals, preferably humans and other organisms, including as a result of the biological activity of a labyrinth voltage-dependent sodium channel, Or any human disease and condition that can be ameliorated by modulating the biological activity of a voltage-dependent sodium channel. As defined herein, a disease or condition mediated by a sodium channel refers to a disease or condition that is ameliorated in the preparation of a nanochannel in a mammal, preferably a human, and includes, but is not limited to, pain, central nervous system symptoms, such as neoplastic tumors. , anxiety, depression and bipolar diseases; cardiovascular symptoms such as irregular rhythm, atrial fibrillation and ventricular fibrillation; neuromuscular symptoms such as restless foot syndrome steaming and muscle plague or tetanus; resistance to stroke, nerve damage and Multiple sclerosis neuroprotection; and channel disease, such as acral red pain and familial rectal pain syndrome. 143924-sp-2009 ll27-l-127-201020257: This invention relates to compounds, pharmaceutical compositions, and methods of using the same and pharmaceutical compositions for treating sodium channel-mediated diseases in mammals, preferably humans. And preferably related to painful diseases, middle treading symptoms, such as epilepsy, anxiety, depression and bipolar diseases; cardiovascular symptoms such as irregular rhythm, atrial fibrillation and ventricular fibrosis; diminished muscle symptoms '譬 不 restless foot syndrome and muscle paralysis or tetanus; nerve protection against stroke, nerve damage and multiple sclerosis; and channel disease, such as limb red pain and familial rectal pain (four), the way is to Φ A mammal, preferably a human, in need of such treatment, is administered an effective amount of a sodium blocker to modulate (especially inhibit) the agent. Thus, the present invention provides a method of treating a mammal or protecting a mammal from the development of a sub-channel-mediated disease (especially a method comprising administering a therapeutically effective amount to a milk-drinking animal, especially a human, in need thereof) A compound or a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention wherein the compound modulates the activity of one or more voltage-dependent sodium channels.

Q The general value of the compounds of the invention in the medium, especially the nanochannel ion flux, can be determined using the assays described below in the biological assay section. Alternatively, the general value of the compound in the treatment of symptoms and disease can be broken down in a standard animal model for confirming the efficacy of the compound in the treatment of pain. Animal models of human neuropathic pain symptoms have been developed which can cause reproducible sensory deficits (hyperalgesia, hyperalgesia, and spontaneous pain)' over a period of time that can be assessed by sensory testing. By establishing the degree of sensory abnormalities and hyperalgesia caused by mechanical, chemical and temperature conditions, several physiological and pathological symptoms found in humans can be modeled as 143924-SP-20091127-1 •128· 201020257' Allow evaluation of medications. In the rat model of peripheral nerve injury, the ectopic activity in the injured nerve corresponds to signs of pain behavior. In these modes, the intravenous application of the nanochannel blocker and the local anesthetic lidocaine can suppress ectopic activity and reverse tactile sensation abnormalities without affecting the concentration of general motor function (Mao, J). And chen, LL, Pain (2000), 87: 7-17). The ratio of the effective dose to the body shape in these rat models is converted to a dose that is proven to be effective in humans (Tandian, D L. and Br〇se, wg., ® (1991), 74(5) : 949-951). Furthermore, Lidodenn® lidocaine, which is applied as a skin patch, is currently an FDA-approved treatment for post-herpetic neuralgia (Devers, A and Glaler, B s, CU Brain (2〇〇〇), 16(3) :205-8). Diseases or symptoms mediated by sodium channels also include pain associated with HIV, neuropathy caused by HIV treatment, tri-analgia, lingual and pharyngeal neuralgia, neuropathy with metastatic infiltration, pain in obesity, and thalamic injury咼Blood pressure, autoimmune diseases, asthma, drug addiction (such as opiates, benzodiazepine, amphetamine, coca test, alcohol, smoldering inhalation), Alzheimer's disease, dementia, and aging Associated memory loss, K〇rsak〇ff syndrome, restenosis, urinary dysfunction, incontinence, Parkinson's disease, cerebral vascular dysfunction, neurosis, gastrointestinal disease, sickle cell anemia, transplant rejection, heart failure , myocardial infarction, reperfusion injury, intermittent claudication, colic, sputum, respiratory disease, brain or myocardial insufficiency, long _QT sign, catechin, urinary multi-type ventricular tachycardia, eye disease, paralysis , spastic paraplegia, myopathy, myasthenia gravis, congenital myotonic rickets, 143924-sp-20091127-1 -129- 201020257 hypercalcemia periodic paralysis, hypokalemia periodic hemp , baldness, anxiety, mental illness, mania, paranoia, seasonal affective disorder, fear disorder, obsessive-compulsive disorder (OCD), phobia, loneliness, __ syndrome town, Retts syndrome town, collapse illness, Attention deficit disorder, aggressiveness, impulsive control disorder, thrombosis, pre-clamping, congestive heart failure, cardiac arrest, Freidrich's disorder, spinal cord and cerebellar disorders, myelopathy, radiculopathy, systemic lupus erythematosus, Granulomatous disease, olive body _ pons - cerebellar atrophy, spinal cord and cerebellar disorders, incidental disorders, muscle fibrillation, progressive pale globus atrophy, progressive pruritus and sputum, _ traumatic brain injury, Cerebral edema, hydrocephalus injury, spinal cord injury, anorexia nervosa, good hunger, Prader-Willi syndrome, obesity, optic neuritis, cataract, vision, 'membrane hemorrhage, refractory retinopathy, retinitis pigmentosa, acute and Chronic glaucoma, speckle degeneration, retinal artery occlusion, chorea, Huntington's disease, cerebral edema, proctitis, post-acne neuralgia, Frequent pain, heat sensitivity, sarcoidosis, irritating intestinal syndrome, Durard syndrome, Podner's syndrome, Brngado syndrome, Liddle syndrome 'Clone' disease, multiple sclerosis and multiple Hardening (MS) associated pain, tendon Atrophic lateral sclerosis (ALS), disseminated sclerosis, neuropathy in diabetic patients, peripheral neuropathy, Charcot_Marie dental syndrome, arthritis 'rheumatic arthritis, osteoarthritis, cartilage Limeosis, atherosclerosis, paroxysmal dystonia, muscle weakness syndrome, myotonia, myotonia dystrophy, muscular dystrophy, malignant hyperthermia, gallbladder fibrosis, pseudoaldosteronism, rhabdomyolysis, Mental disorders 'hypothyroidism, bipolar depression, anxiety, schizophrenia, sodium channel toxin-related diseases, home 143924-SP-20091127-1 -130- 201020257 ethnic acral red pain, primary limb red pain Disease, rectal pain, cancer, epilepsy, partial and general tension episodes, fever episodes, absence seizures (sickness episodes), myoclonic episodes, no tension episodes, Array attack, Gu,

WeStSynd〇me (infant sputum), multiple resistance seizures, seizure prevention (anti-problem seizures), familial Mediterranean heat syndrome town, gout, restless foot stagnation, irregular rhythm, fibromyalgia, stroke due to stroke Or neurological protection caused by nerve damage, rapid rhythm, atrial fibrillation and ventricular fibrillation, and general or local anesthetics. #的金融文,, pain words, refers to all kinds of pain, and is considered to include but not limited to neuropathic pain, inflammatory pain, nociceptive pain, spontaneous pain, neuropathic pain, mouth pain, burns Pain, burning mouth syndrome, somatic pain, visceral pain, muscle pain, toothache, cancer pain, chemotherapy pain, injury pain, surgical pain, postoperative pain, production pain, labor pain, reflex sympathetic dystrophy Symptoms, brachial plexus tears, neurogenic bladder, chronic pain, persistent pain, pain in the distal sputum, pain in the media, acute pain (eg musculoskeletal and postoperative pain), chronic headache, migraine, Familial hemiparex, symptoms associated with headache, sinus node headache, nervous headache, imaginary limb pain, peripheral nerve injury, post-stroke pain, thalamic injury, radiculopathy, spleen pain, post-surgical pain, non-cardiac Chest, irritating bowel syndrome, and pain associated with intestinal disorders and dyspepsia' and combinations thereof. In addition to pain, sodium channel blockers have clinical utility. Epilepsy and heart rhythm are often the target of sodium channel blockers. According to the recent evidence of the automatic substance mode, it is pointed out that the sodium channel blocker can also be caused by multiple strokes in the 174924-sp-20091127-1 -131 - 201020257 due to stroke or nerve injury. (MS) is used for neuroprotection in patients (Clare, JJ et al., filial piety in the above, and Anger, Ding et al., cited above. The present invention also relates to compounds, pharmaceutical compositions, And methods of using such compounds and pharmaceutical compositions for treating or preventing a disease or condition, such as benign prostatic hyperplasia (BPH), hypercholesterolemia, cancer, and scrapie (itch). Benign prostate hyperplasia (BPH) ), also known as benign prostatic hypertrophy, is one of the most common diseases affecting aging men. BPH is a progressive symptom characterized by a large knot of prostate tissue, causing obstruction of the urethra. It may include an increase in the bladder smooth muscle hypertrophy, decompensated bladder dislocation, acute urinary retention, and urinary tract infection. Human BPH has a high public health impact and is the most common cause of surgical intervention in older men. - An attempt has been made to clarify the etiology and pathogenesis' and thus experimental models have been developed. Spontaneous animal models are restricted to black-collared dogs and dogs. There are many common features in human and dog facial systems. In both species, the development of BPH occurs naturally with the age of progression and can be prevented by castration during early/pre-existing period. © for surgery © Medical alternatives are highly desirable for the treatment of BHP and its effects The prostate epithelial hyperplasia in both males and dogs is characterized by androgen-sensitive taste accompanied by degeneration of androgen loss, and epithelial hyperplasia when androgen is replaced. Cells from the prostate It has been shown to exhibit high levels of voltage-selected sodium channels. Immunostaining studies clearly document the injection of voltage-sampling sodium channels in prostate tissue (p consider (10) exo-mineral tears 2005; 8(3): 266-73) 〇' 143924-sp-20〇9! 127-1 -132- 201020257 High cholesterol, meaning elevated blood cholesterol, such as atherosclerosis, stenosis, blood fat Too much, stroke, too much, high The development of stress, obesity, diabetes, cardiovascular disease (CVD), myocardialism, and heart attack is an established risk factor. Therefore, it is known to reduce total serum cholesterol in individuals with high cholesterol levels. It will reduce the risk of these diseases. The reduction of low-density lipoprotein cholesterol is a necessary step in the prevention of CVD. Although there are a variety of hyperbilirutory therapies, there is a continuing need in this field of technology and continuous search for alternatives. Therapeutic Therapy The present invention provides compounds which are useful as anti-hypercholesterolemia agents, and their associated symptoms. The compounds of the invention may act in a variety of ways. Although not wishing to be bound to any particular mechanism of action, the compounds may be A direct or indirect inhibitor of the enzyme thiol-based CoA··cholesteryl thiol transferase (ACAT), which causes inhibition of cholesterol esterification and transport across the intestinal wall. Another possibility may be that the compound of the invention may be a direct or indirect inhibitor of cholesterol biosynthesis in the liver. It may be the case that some of the compounds of the invention may be used as both direct or indirect inhibitors of ACAT and cholesterol biosynthesis. Scrapie, commonly known as itching, is a common skin condition. Although the exact cause of scrapie is complex and lacking in understanding, it has long been recognized as having a parental interaction with pain. In particular, the salty recognition channel mostly conveys or spreads the itching signal along the skin along the axis. The transmission of the lacquer pulse will be a feeling of uncomfortableness for 7 people, which will induce a need or reflection for scratching. From the level of neurobiology, it is generally believed that there is a common complexity of specific mediators, 143924-sp-20091127-1 201020257 = neuronal pathway and central process of snoring and pain, and recent data refers to pain - associated with pruritus There is a width between the terminal mediators and/or receptors (Nature Reviews Neuroscience, 7 ··535-547, 2QQ6). Significantly, 'pain and sequelae' have similar mechanisms of neuronal sensitization in the peripheral gods (four) and central gods (four), but also show plot differences. For example, mild painful stimuli from scratching are sensible in the sense of dying. In contrast, analgesics such as opioids can cause severe paralysis. Antagonistic interactions between pain and pain can be treated with pruritus, and current research focuses on the identification of future analgesics and painkillers. The compounds of the present invention have been shown to have an analgesic effect in many animal modes at oral doses ranging from 1 mg/kg to mg/kg. The compounds of the invention are also useful in the treatment of scrapie. Types of pruritus or skin irritation include, but are not limited to: a) pruritus, itch caused by hemodialysis, prion prion, and skin disorders (eg, contact dermatitis)' systemic disorders, neuropathy, Itching caused by psychogenic factors or a mixture thereof; ❹ b) itch caused by allergic reactions, insect bites, allergic (eg dry skin, acne, eczema, psoriasis), inflammatory symptoms or injuries; c ) itch associated with vaginal vestibulitis; and d) skin irritation or inflammatory effects from administration of another therapeutic agent, such as antibiotics, antiviral agents, and antihistamines. The compounds of the invention may also be used in the treatment of mammals, preferably humans, for the treatment or prevention of certain hormone-sensitive cancers, such as prostate cancer (adenocarcinoma), breast cancer, 143924-sp-20091127-l-134-201020257 ovarian cancer , testicular cancer, thyroid tumor formation. The voltage-gated sodium channel has been shown to be in the prostate and breast cancer cells. The up-regulation of nascent Nav 1.5 occurs in human breast cancer as an integral part of the metastatic process and can simultaneously serve as a novel marker for metastatic phenotypes and therapeutic targets (C7k ameer to. August 1, 2005) ;11(15) : 5381-9). The functional characterization of the voltage-selective sodium channel, especially the Navl.7, is accompanied by a strong metastatic potential in prostate cancer (CaP). Voltage-sampling sodium channel 仏 subunit immunostaining, using antibodies specific to the sodium channel ^^ subunit, : the lineage in the prostate tissue is significant 'and significantly stronger in Cap relative to non-(10) patients Oz bribe Pm Coffee.c edition, 2005; 8(3): 266-73). The compounds of the present invention are also useful in the treatment or prevention of conditions such as, but not limited to, acute urinary retention and urinary tract infections in dairy animals. The compounds of the present invention are also useful for treating or preventing certain endocrine balance deficiency or endocrine diseases such as congenital adrenal hyperplasia, thyroid functioning, hypothyroidism, osteoporosis, osteomalacia, rickets, Cushing's sign (4), C Hypertrophy of _ syndrome, hypogonadism, hypergonadism, infertility, fertility and diabetes. The present invention is susceptible to providing a pi π π + (4) ...... in the same manner to confirm that it can be used as a therapeutic mitigation modulation. Sodium channels (IV) In vitro and in vivo assays, for example: using a variety of metric ions and measuring electricity > melon, degree 1 membrane potential, and sputum weight (such as sodium or transcript content, and use case 2 Concentration, measurement of second agent and patch clamping electrophysiology. Pressure sensitive dyes, radioactive display longitudinal-species such cases involve screening chemicals for the modulation of sodium channel activity 143924-SP-20091127-1 - 135 - 201020257 Ability, then confirm its use as a modulator. In Bean et al., GenemZ P/iFioZog); (1983), 83: 613-642 and Leuwer, Μ. et al., Price /. (2004), 141 (1 ): The typical test described in 47-54 uses patch clamping techniques to study the behavior of the channel. Such techniques are known to those skilled in the art and can be developed into low or medium throughput assays using current techniques to assess the ability of a compound to modulate its sodium channel behavior. Competitive binding assays using known sodium channel toxins, such as tetrodotoxin, alpha- scorpion toxin, aconitin, BTX, etc., are suitable for use in identifying potential therapeutic agents with high selectivity for a particular sodium channel. The use of lanthanide in such binding assays is known and described in McNeal, Ε.Τ. et al., /. Med (1985), 28(3): 381-8; with Creveling, CR et al. , #.经存学J:之才法, 农八卷.·妒经# #(Conn PM版) (1992), pp. 25-37, University Press, New Yoirk. Such assays can be performed in a natural endogenous environment or in a recombinant environment in cells or cell or tissue extracts that express channels of interest to us. Tests that can be used include plate detection, which measures Na+ influx through surrogate markers, such as 14C-胍 influx, or cell depolarization, using fluorescent dyes such as FRET, and other fluorescent Detection or radiolabel identification test, using radioactive labeling of aconite, BTX, TTX or STX. More direct measurements can be performed manually or by automated electrophysiology systems. The influx detection is explained in more detail in the biological testing section below. The throughput of the test compound is an important consideration in selecting the test to be used. In some strategies, hundreds of thousands of compounds 143924-sp-20091127-1 -136- 201020257 In the case of being tested, a private T u 1 is not expected to use a low throughput approach. However, in other cases, low yields satisfactorily identify important differences between a limited number of compounds. M赍v Α σ ' , & 10 must combine the detection types to confirm specific sodium channel modulation compounds. The electrophysiological test using the patch-clamp technique is purely accepted as the gold standard for the detailed interaction of the serotonin channel compound, and as Bean et al., in the work cited above, 舆. Quoted above.手动 A manual low-throughput screening (LTS) method that compares 2-10 compounds per day Φ; a recently developed system for automated medium throughput screening (MTS) with 2〇_5〇 patches per day (meaning compound) under 'and from the technology of the company of Sunnyvale, CA, which allows automated high throughput screening (HTS), 1 〇〇〇 3 patches per day (meaning compound )under. An automated patch-clamping system utilizes planar electrode technology to accelerate the rate of drug discovery. The planar electrode system is capable of achieving high electrical resistance, and the cell-attached seal is followed by a stable, low-noise whole-cell recording that can be compared to conventional records. The appropriate instrument is the PatchXpress 7000A (Axon Instruments, Union City, CA). A variety of cell lines and culture techniques, including adherent cells and cells that grow spontaneously in suspension, are graded to provide seal success and stability. Immortal cells that exhibit a high degree of associated sodium ion channels (e.g., HEK and CHO) can be conjugated to high density suspension cultures. Other tests can be selected that allow the investigator to identify compounds that block the state of a particular channel, such as an on state, a off state, or a standstill state, or 143924-sp-20091127-1 -137 - 201020257 which blocks from on to off, Close to the transition from standstill or standstill to on. Those skilled in the art are generally familiar with such tests. Combined detection can also be used, but these have only a limited amount of functional value and information. The design includes a combination of conventional radioactive filter-based detection or a focus-based fluorescent system available from the Evotec OAI Group of Companies (Hamburg, Germany), both of which are HTS. Radioactive flux detection can also be used. In this test, the channel is activated by stimulation with veratridine or aconitine, and the toxin is kept in a stable state, and the channel blocker is prevented by its ability to prevent ion inflow. confirm. This test utilizes radioactive 22 [Na] and 14 [C] phosphonium ions as an extender. The FlashPlate & Cytostar-T plate in live cells avoids the separation step and is suitable for HTS. The scintillation panel technology has also advanced this approach to HTS suitability. Due to the functional aspects of this test, the amount of information is reasonably good. Yet another format uses the FLIPR System Membrane Potential Kit (HTS) to measure the redistribution of membrane potential, which is available from Molecular Dynamics (a division of Amersham Biosciences, Piscataway, NJ). This method is limited to slowing membrane potential changes. Some problems can be caused by the fluorescent background of the compound. The test compound can also directly affect the fluidity of the cell membrane and lead to an increase in intracellular dye concentration. Due to the functional aspects of the detection, the amount of information is reasonably good. Sodium dyes can be used to measure the rate or amount of sodium ions flowing through the channel. This type of test provides an extremely high amount of information about potential channel blockers. This test is functional and directly measures Na+ influx. CoroNa red, SBFI and/or sodium green (Molecular Probes, Eugene OR) can be used to measure Na 143924-sp-20091127-1 -138- 201020257 influx; all are Na responsive dyes. It can be combined with FLIPR instruments. The use of such dyes in screening has not been previously described in the literature. Calcium dyes also have potential in this format. In another test, a FRET-based voltage sensor is used to measure the ability of the test compound to directly block Na influx. Commercially available HTS systems include the VIPRTM II FRET system (Aurora Biotech, San Diego, CA, a division of Vertex Pharmaceuticals), which can be used with FRET dyes - which are also available from Aurora Biotechnology. This test measures the Φ sub-second response to voltage changes. No need to change the channel function. This test measures depolarization and hyperpolarization and provides a proportional output for quantification. The slightly less expensive MTS variant of this test is FLEXstationTM (Molecular Devices) with FRET dyes from Aurora Biotechnology. Other methods of testing the compounds disclosed herein are also known and available to those skilled in the art. These results provide the basis for analyzing the structure-activity relationship (SAR) between the test compound and the sodium channel. Certain substituents on the core structure of the compound to be tested help to provide more potent inhibitory compounds. SAR analysis is currently one of the tools available to those skilled in the art to confirm that preferred embodiments of the compounds of the invention are useful as therapeutic agents. The thus-confirmed modulator is then tested in a variety of in vivo modes to determine if it will alleviate pain, especially chronic pain or other symptoms such as irregularities and epilepsy, benign prostatic hyperplasia (BPH), high Cholesterol, cancer, and scrapie (itch) are accompanied by the least adverse events. The assays described below in the biological assay section can be used to assess the biological activity of the compounds of the invention 143924-SD-20091127-1 -139. 201020257. Typically, the successful therapeutic agents of the present invention will meet some or all of the following criteria. Oral use should be at or above 20%. Animal mode efficacy is less than about 0.1 micrograms to about 100 milligrams per kilogram of body weight, while standard human doses range from 0.1 micrograms to about 1 milligram per kilogram of body weight, except for doses outside this range that are acceptable milligrams per second. Kg " means the number of milligrams of compound per kilogram of body mass that is administered to the patient). The therapeutic index (or the ratio of the amount of poisoning to the therapeutic dose) should be greater than 100. The efficacy (when expressed by the IC5 〇 value) should be less than 1〇_, preferably less than 1, and the best is less than 5〇 nM. Inhibitory Concentration 50%") is a measure of the amount of compound required to achieve 50% inhibition of ion flux through the sodium channel over a specified period of time in a test of the present invention. The compounds of the invention have been shown to range from less than one nanomolar to less than one micromolar. In an alternative use of the invention, the compounds of the invention may be used for in vitro or in vivo studies, As an exemplifying agent, for comparison (4), to find other compounds which can also be used for treating or protecting (4) the various diseases disclosed in the present invention. The present invention relates to a biological sample or a mammal (preferably a human). Inhibition of NavU, Navl.2, NavU, Ν~14, NavL5, 灿0.6, ^^^^^".^^^"."^^, this method includes 'being better for humans, The compound of formula j or a composition comprising the compound or the biological sample is contacted therewith. The term "biological sample" as used herein includes, but is not limited to, cell cultures or extracts thereof; biopsies obtained from mammals or their extracts; and blood, saliva, urine Wing 143924-sp-20091127-1 201020257 Toilet, semen, tears or other body fluids or their extracts. Biological sample NavL1, Navl.2, NaV1.3, Navl.4’Navl.5’Nai6

Na:l.7, Nav! ·8 or Nay! .9 inhibition of activity, can be used to familiarize with this artist: know ^ variety of #. Examples of such purposes include, but are not limited to, sodium ion channels in the study of 0 biological and pathological phenomena. u Novel Nano-Ion Channel Inhibitors The compounds of the invention as set forth above in the Summary of the Invention

Isomer: a palmo isomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable salt, solvate or prodrug thereof, and/or a pharmaceutical composition herein, comprising An excipient as hereinbefore, and/or a plurality of compounds of the invention as set forth above in the Summary of the Invention, a construct, a palmomer, a tautomer or a mixture thereof, or a pharmaceutically acceptable: acceptable Salts, solvates or prodrugs can be used in the preparation of a medicament for the treatment of a disease or condition in the sodium channel (4) in a mammal. Pharmaceutical Compositions and Administration of the Invention The invention also relates to a compound comprising a compound of the invention as disclosed herein. In a particular embodiment, the invention relates to a composition comprising a compound of the invention in a pharmaceutically acceptable excipient, carrier or diluent, and when administered to an animal, preferably In mammals, optimally in humans, the amount can be effectively modulated, preferably by inhibiting the ion flux through a voltage-dependent (four) way to treat diseases mediated by the nanochannel, such as pain. The administration of the compound of the present invention or a pharmaceutically acceptable salt thereof in pure form or in a suitable pharmaceutical composition can be carried out by any of the accepted modes of administration for the administration of a similarly useful agent. The pharmaceutical composition of the present invention is prepared by combining 143924-sp-20091127-1 141-201020257 a compound of the present invention with a suitable pharmaceutically acceptable carrier agent, and can be formulated into a formulation, in the form of a solid or a form or Typical routes for gaseous pharmaceutical compositions such as tablets, capsules, powders, granules = sedatives, injections, inhalations, gels, microspheres and aerosols include, but are not limited to. Widely foreskin, inhalation, non-«, sublingual, rectal, yin = 2 = the term parenteral used, including, injection or irrigation in this article, 'main skills street road intramuscular, sternum... The invention The pharmaceutical composition is formulated so as to allow the active ingredient to be taken as a raw unit or a composition of the patient when the composition is administered to the patient. The agent may be a single-dosage unit, and the container in which the compound of the present invention is aerosol-soluble may hold a plurality of dosage units. The actual method of preparing such a dosage form is known to those skilled in the art, for example, see shoulder/痹存学舆紫, with the College of Science. The person who wants to be given the object / (Philad_a pharmaceutically effective * the compound of the invention or its two = = contains the treatment of the invention to treat the disease or symptoms of interest to us According to the following: The pharmaceutical composition for use herein also contains a pharmaceutically acceptable to the individual receiving the composition: the anti-wound itself does not cause π. The amphibious agent, and it has no undue toxicity. Carriers accepted include, but are not limited to, liquids, 譬m ethanol, and the like. Pharmacologically acceptable carrier, Dilution Science, Inc., N.:: line 143924-sp-2009ll27-l • 142* 201020257 The pharmaceutical composition of the present invention may be in solid or liquid form. The carrier is microparticles, so that the combination The system may be, for example, a tablet or a powder, and the composition may be, for example, an oral syrup, and the injectable solution may be used, for example, as an aerosol for administration by inhalation. The pharmaceutical composition is preferably solid when administered as a drug. Or a liquid form in which the semi-solid, semi-liquid, suspension, and gel forms are included in the form of solid or liquid herein. e:: a solid composition for oral administration, a pharmaceutical composition can be Formulated into a final form, granules, compressed tablets, pills, capsules, chewing gum, flats, etc. Such solid compositions typically contain one or more inert diluents or edible carriers. In addition, or a plurality of the following may be Exist. Adhesives '譬 domain methyl cellulose, ethyl cellulose, micro cellulose, corn starch, etc.; moisturizing such as colloidal cerium oxide such as peppermint, sassafras or gelatin; excipients譬如殿粉, lactose or dextrin Γ disintegrator, such as alginic acid, sodium alginate, Primogei slip agent, such as magnesium stearate or sterotex; glidant 矽; sweeteners, such as sucrose or saccharin, flavoring agent A series or orange flavoring agent; and a coloring agent. When the pharmaceutical composition is in the form of a gel, or a gelatin capsule, such as a gelatin capsule, it may contain a liquid carrier in addition to the above types of substances. For example, polyethylene glycol or oil. The pharmaceutical composition may be in the form of a liquid, such as an elixir, syrup, solution, emulsion or suspension. This liquid may be administered orally, or by injection, as two An example of a preferred composition, in addition to a compound of the invention, contains - or a plurality of sweeteners 'preservatives' dyes/coloring 143924-sp-20091127-1 • 143-201020257 and astringent enhancement when intended for oral administration. Agent. In the compositions intended for administration by injection, various surfactants, preservatives, wetting agents, dispersing agents, suspending agents, granules, stabilizers and isotonic agents can be added. The liquid pharmaceutical composition of the present invention, whether in the form of a solution or suspension, may comprise one or more of the following adjuvants: a sterile diluent: Lu, such as a water for injection, a saline solution, preferably a physiological saline solution. Ringer's gas-filled, non-volatile oil, such as synthetic mono- or diglycerin, can be used as a solvent or suspension medium 'polyethylene glycol, glycerol' propylene glycol or other agents; antibacterial agents, such as mellow alcohol or For methyl benzoic acid methyl ester; antioxidants such as ascorbic acid or sodium bisulfite; integrators, such as sputum, such as acetate, citrate or phosphate, and the preparation of 4 agents such as gasification Sodium or dextrose. Parenteral preparations == Ampoules made of glass or plastic, disposable syringes or compounds are preferably sterile. ^ "Preferred adjuvant. Injectable pharmaceutical group ❹ ::: The liquid pharmaceutical composition of the present invention for enteral or oral administration should contain the compound of the present invention such that an appropriate dose will be obtained. Typically, ... is at least 〇.〇 1% of the compound of the present invention is in the form of a drug, and the amount may be between α1 and about 70% by weight of the composition. The oral pharmaceutical composition contains about 4% of the composition of the present invention. The preferred pharmaceutical compositions and formulations of the present invention are prepared such that the parenteral dosage unit contains from _ to 10% by weight of the pharmaceutical composition of the present invention may be intended for topical administration prior to dilution. Medium ' 143924-sp-2009l 127-1 -144- 201020257 The carrier may suitably comprise a solution, emulsion, ointment or gel base. For example, the base may comprise one or more of the following: paraffin oil, lanolin , polyethylene glycol bee, mineral oil, thinner, such as water and alcohol, and emulsifiers and stabilizers. Thickeners may be present in pharmaceutical compositions for topical administration. If i, transdermal administration, then combination The substance may include a transdermal patch or an iontophoresis device. The formulation may contain a concentration of the compound of the present invention of from about 1 to about (1)% by weight per unit volume. The pharmaceutical composition of the present invention may be intended for rectal administration, for example, in the form of a suppository, which will melt in the rectum. And releasing the drug. The composition for rectal administration may contain an oleaginous base as a suitable non-irritating excipient. Such binders include, but are not limited to, lanolin, cocoa butter, and polyethylene glycol. The pharmaceutical compositions of the invention may comprise a variety of materials which modify the physical form of the solid or liquid dosage unit. For example, the composition may comprise a material which will form a coating shell surrounding the active ingredient. The material forming the coating shell is typically inert. And may be selected, for example, from sugars, shellac and other enteric coating agents. • Or 'the active ingredient may be contained in a gelatin capsule. The pharmaceutical composition of the present invention in solid or liquid form may comprise one that will be incorporated into the present invention. A compound, and an agent for assisting in the delivery of a compound. Suitable agents that can function in this capacity include single or multiple antibodies, proteins or vesicles. The pharmaceutical composition comprises a dosage unit which can be administered by aerosol to a system for representing a variety of systems, ranging from a colloidal nature to a system containing pressurized packaging. Transmission can be by liquefaction or compression. Gas, or by a suitable pump system that will dispense the active ingredient. The gas soluble 143924-sp-20091127-1 -145- 201020257 of the compound of the invention can be transported in an early phase, two phase or three phase system to transport the live sol: The transmission includes the necessary container 'actuator, valve, ya, etc. It can be used to form the kit 1 and the artist has no (4) ^ good aerosol. The concept is that the pharmaceutical composition of the invention can be obtained by medical technology. The above-described methods of operation such as 'pharmaceutical compositions intended for injection by injection are combined with sterile distilled water to form a solution to form a surfactant to aid in the formation of a homogenous solution or suspension. Interface: 2 agents are compounds that interact with the compounds of the invention in a non-covalent manner to facilitate the dissolution or "floating" of the valvular in an aqueous delivery system. ❹ / the inventive compound or a pharmaceutically acceptable salt thereof The therapeutically effective amount =, which will vary according to a variety of factors 'including the specific compound used: sex; the metabolic stability and length of the compound; the age of the patient, the body-like health, the sex diet; Formula and time; excretion rate; drug combination; specific disease 'symptom m and treated patients. In general, the therapeutically effective dose is about 嶋mg/kg (for 70 kg mammals) This means: 〇7 mg) to about two: /A kg (meaning 7. gram); the therapeutically effective dose is preferably (for 70 kg of mammals) about __ kg (meaning 〇7 mg) ) to about 5 mg / kg (jt is 3.5 g), the therapeutically effective dose is better (for 7 kg kg of re-infant animals) about 1 mg / kg (meaning 7 mg) to about 25 mg / Kilograms (meaning 175 grams). The range of doses provided in this article is not intended. It becomes a limit, and it represents the preferred dose range. However, the 'optimal dose is for 143924-sp.2〇〇9l 127-1 •146- 201020257 for individual patients. And measurable (see, for example, Berkow et al., Aferc^; Handbook, 16th edition, Merck, Rahway, NJ, 1992 'Goodmanetna's Goeo/mizn Code OYma«戌居学学竣, 10th edition, Pergamon Publishing Company, Elmsford, NY, (2001); Principles and Practice of Drug Therapy · Clinical Pharmacology and Therapeutics, %, ADIS Publishing Company, _ Williams and Wilkins, Baltimore, MD. ( 1987), Ebadi, #遂学, Little, Brown, Boston (1985); Osolci al., ed. and emiwgion 戌##存#, 18th edition, Mack Publishing Company (Easton, PA) (1990); 〇Katzung , ed., ed., et al., Appleton and Lange, Norwalk CT (1992). The total dose required for each treatment can be administered by multiple doses or in a single dose over the course of the day (if needed). In general, the treatment begins with a smaller dose, Lower than the optimum dose of the compound. The dose is then increased by small increments until the optimum effect is achieved under such conditions. The diagnostic pharmaceutical compound or composition can be used alone or in combination with the pathological disease or against Other diagnostic agents for other pathological conditions and / ® or pharmaceutical administration. The recipient of the compound and/or composition of the invention may be administered to any vertebrate, such as a mammal. In mammals, preferred recipients are primate (including humans, apes and monkeys), cloven-hoofed animals (including horses, goats, cows, sheep, pigs), rodents (including mice). , mammals, rabbits and big hamsters) and mammals of carnivores (including cats and dogs). Among birds, preferred recipients are turkeys, chickens and other members of the same family. The best recipient is human. For topical application, it is preferred to administer an effective amount of the composition according to the invention 143924-SP-20091127-1 -147· 201020257 to the target area 'eg skin surface, mucous membrane, etc., which is adjacent to the treatment A few peripheral nerves. In general, the amount of the compound is from 1 mg to about 1 g of the compound of the present invention, depending on the area to be treated, for diagnosis, prevention or treatment, the severity of the disease and the locality used. The nature of the agent. Preferably, the topical formulation is an ointment wherein from about 0.001 to about 5 mg of active ingredient per ounce of cream base. The pharmaceutical composition can be formulated as a transdermal composition or a transdermal delivery device ("patch"). Such compositions are lined with active compound reservoirs, control membranes, liners, and contact adhesives. Such transdermal patches can be used to provide continuous pulsation or to deliver the compounds of the invention as desired, as desired. The compositions of the present invention can be formulated by the use of procedures known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a patient. The controlled release drug delivery system includes an osmotic pump system and a dissolution matrix 3 reservoir-coated reservoir or drug-polymer matrix formulation. An example of a controlled release system is shown in U.S. Patent 3,845,77, 〇 七 风 仍 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , The composition of Guangming can also be transmitted through the intranasal drug delivery system for topical system and nose to brain medical therapy ^ controlled particle dispersion (cpD)TM technology, traditional nasal spray, inhaler or atomization can It is known to those skilled in the art to provide effective local and systemic delivery of the drug in the form of an olfactory region and paranasal sinuses. The present invention also relates to a vaginal capsid or nucleus suitable for administration to a female human or animal. Core drug delivery device. The device may comprise an active pharmaceutical ingredient in a matrix of polymer 143924-SP-20091127-1 -148- 201020257, surrounded by a sheath, and capable of being released on a per-twist basis in a substantially zero-order version Compounds, similar to those used to apply anthrone, as described in PCT Publication No. WO 98/50016. Current methods for ocular delivery include topical administration (eye drops), combined sub-injection, periocular injection, glass In vivo injections, surgical implants, and iontophoresis (using small currents to deliver ionized drugs into and through body tissues). Those skilled in the art will combine the best suitable excipients with the compound to provide safe and effective Intraocular administration. φ The most suitable route depends on the nature and severity of the symptoms being treated. Those who are familiar with this art are also familiar with the method of administration (oral, intravenous, inhalation, subcutaneous, rectal, etc.), dosage form, and appropriate medical form. Agents and other matters associated with delivery of the compound to a patient in need thereof. Combination Therapy The compounds of the invention may be used in combination with one or more other compounds of the invention or one or more other therapeutic agents or in any combination thereof to treat a nanochannel Diseases and Symptoms of the Agent. For example, the compounds of the present invention may be administered in combination with other therapeutic agents, simultaneously, sequentially or separately, including but not limited to: • Opiate analgesics such as morphine, heroin, cocaine, oxygen Kemorphin, levorphanol, levallorphan, oxycodone, Codeine, dihydrocodeine, propoxyphene, nalmefene, fentanyl, dihydrocodeine hydrazine, hydromorphone, meripidine, Metha _ (methadone), propylene, 非, naloxone, naltrexone, buprenorphine, circumcision, 143924-sp-20091127-1 -149- 201020257 nalbuphine and pentazocine; • non-opioid analgesics, such as acetomeniphen, salicylate (eg aspirin); • non-steroidal anti-inflammatory Drugs (NSAID), such as ibuprofen, naproxen, fenoprofen, ketoprofen, celecoxrt, eclipse Diclofenac, diflusinal, etodolac, biphenylbutyric acid, fenoprofen, flufenisal, fluorodipropione, iso Ibuprofen, indomethacin, ketoprofen, ketoprofen Ketorolac, sulphuric acid, sulphuric acid, meloxicam, nabumetone, naproxen, nimesulide, sirolifloxacin, ou Osalazine, 4 oxaprozin, phenylbutazone, piroxicam, sulfasalazine, sulindac, tetraphenyl ρ to met acetic acid (tolmetin) and zomepirac (zomepirac); • antispasmodic drugs, such as amine methotrexate, carboxynitrate heptatriene, lamotrigin, lamotrigine, palmiperate, Topiramat, gabapentin, and pregabalin; • antidepressants such as tricyclic antidepressants such as amitriptyline and clofidamine Clomipramine), despramine, propanol p and nortriptyline; • COX-2 selective inhibitors such as celecoxib, rofecoxib ), parecoxib, vidkusibi 143924-SP-20091127-1 -150-

(S 201020257 (valdecoxib), deracoxib, etoricoxU3, and lumiracoxib; • <2-adrenergic drugs, such as doxazosin ), tasulosin, clonidine, guanfacine, dexmetatomidine, modafinil, and 4-amino-6,7-di Methoxy-2-(5-methyl succinylamino-1,2,3,4-tetrahydroiso-p-quinolin-2-yl)-5-(2-p-pyridyl)><»林; • Barbiturate sedatives such as amobarbital, dilute isopropyl barbital, sec-butyl barbital, Butabital, hair salon Mephobarbital, metharbital, methohexital, pentobarbital, phenobartital, secobarbital, talbutal, Theamylal and thiopental; • tachykinin (NK) antagonists, particularly NK-3, NK-2 or NK-1 antagonists, such as (aR, 9R)-7- [3,5-bis(trifluoromethyl)benzyl]-8,9,1 0,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7Η-[1,4]diazaoctacene[2,lg][l,7]acridine- 6-13-dione (TAK-637), 5-[[(2R,3S)-2-[(lR)-l-[3,5-bis(trifluoromethyl)phenyl]ethoxy- 3-(4-fluorophenyl)-4-morpholine]methyl]-1,2-dihydro-3H-1,2,4-tris--3-one (MK-869), Ari Aprepitant, lanepitant, dapitant, and 3-[[2-methoxy-5-(trifluoromethoxy)phenyl] guanidino] -2-phenyl-hexahydropyridine (2S, 3S); • coal tar analgesics, especially paracetamol; • serotonin reuptake inhibitors such as Paxi, T (paroxetine), color Sertraline, norfluoxetine (fluoxetine off 143924-SD-20091127-1 -151 - 201020257 methyl metabolite), metabolite demethylsertraline , fluvoxamine, paroxetine, citalopram, citalopram metabolites decoupling citalopram, cityrol (escit) Alopram), d,l-fenfluramine, femoxetine, ifoxetine, cyanodothiepin, litoxetine, Dapoxetine, nefazodone, cericlamine, trazodone, and fluoxetine; • norepinephrine (norepinephrine) reuptake Inhibitors such as maprotiline, lofepramine, mirtazepine, oxaprotiline, fezolamine, tomoxetine , mianserin, buproprion, and buproprion metabolites via hydroxybuproprion, nomifensine, and oxy- ploughing Viloxazine) (Vivalan®), especially selective norepinephrine reuptake inhibitors, such as reboxetine, especially (S, S)-reboxetine, and Wenlafa Venlafaxine, duloxetine-induced neurological disorder Respiratory/anxiolytic agents; • Dual serotonin-norepinephrine reuptake inhibitors, such as venlafaxine, venlafaxine metabolite Ο-demethyl valacin (venlafaxine) ), clomipramine, clomipramine, metabolites, clomipramine, doosil, duloxetine, milnacipran, and C1 m p well; 143924-SO-20091127-1 -152- 201020257 • Acetylcholinesterase inhibitors, such as dopeezil; • 5-HT3 antagonists, such as Ondansetron; • Metabolic glutamate receptor (mGluR) antagonists; • Local anesthetics, such as mexiletine and lidocaine; • corticosteroids such as dexamethasone; • anti-arrhythmic drugs, such as slow heart (mexiletine) with phenytoin; • chelating base antagonists, such as tolterodine, propiverine, tropsium t chloride, darifenacin (darifenacin) ), solitude, solifenacin, TEMiverine and ipratropium; • cannabis-like; • vanilloid-receptor (eg, resinferatoxin) or antagonist (eg capsaicin) Capsazepine)); • sedatives such as phenethidone, ampicillin, methaqualone, and dichloralphenazone; • anxiolytics, such as benzodiazepines, • Antidepressants such as mottazapine, • topical agents (eg lidocaine, capsacin and resiniferotoxin); • muscle relaxants such as benzodiazepines Seven gardens of 'baclofen', carisoprodol, chlorzoxazone, cyclobenzaprine, methocarbamol and orphrenadine • Antihistamine or HI antagonist; 143924-sp-20091127-1 -153- 201020257 • NMDA receptor antagonists; • 5-HT receptor agonists/antagonists; • PDEV inhibitors; • Tramadol® • biliary test (final acid) analgesic; Α-2- 5 ligands; • prostaglandin 2 subtype antagonists; • leukotriene Β4 antagonists; • 5-lipoxygenase inhibitors; and • 5-ΗΤ3 antagonists. Such combinations may be used to treat and/or prevent sodium channels mediated by diseases and conditions including, but not limited to, pain, central and peripheral mediators, acute, chronic, neuropathogenic, and other diseases associated with pain, and others Central nervous disorders such as epilepsy, anxiety, depression, and bipolar disorder; or cardiovascular disorders such as arrhythmia, atrial fibrillation and ventricular fibrillation; neuromuscular disorders such as restless foot syndrome and muscle paralysis or tetanus ; neuroprotection against stroke, nerve damage, and multiple sclerosis; and channel disease 'such as limbal red pain and familial rectal pain, used in this article, combined, refers to - or a variety of compounds of the invention Any mixture or replacement with one or more other compounds of the invention or one or more other therapeutic agents. Unless the context clarifies otherwise, the combination " or the subsequent delivery of the compound of the invention and/or the plurality of chloroforms are also clarified, otherwise the "combination" may include the dosage form of the present invention unless the internal agent is used. Unless otherwise clarified in the text, 'another therapeutic sputum combination may include the 143924-sp-20091127-1-154-201020257: the alternative therapeutic route of the invention. Unless otherwise clarified, The formulation of the compound of the present invention and another therapeutic agent may be included. The method of detoxification and pharmaceutical composition includes, but is not limited to, the kit of parts described in the present invention. The kit of parts also provides a kit containing the pharmaceutical composition. , which comprises one or more compounds of the invention. The kit also includes instructions for utilizing the pharmaceutical composition to modulate ion channel activity, treating pain, and other uses as disclosed herein: commercial packaging A system containing one or more unit doses of a pharmaceutical composition. For example, such a unit dose may be sufficient for the preparation of an intravenous injection. Generally known to those skilled in the art, light and/or Or air sensitive compounds may require special packaging and/or formulation. For example, a package that is opaque to light and/or sealed from contact with ambient air and/or formulated with a suitable coating or excipient may be used. Preparation of ❹ The compounds of the present invention are prepared by the method disclosed herein and by the method described in the patent application WO 2008/046049, which is incorporated herein by reference. The disclosures of which are hereby incorporated by reference in their entirety, in particular in regard to the disclosure of the disclosure of the disclosure of the disclosure of the disclosure of the disclosure of the disclosure of The method of the present invention is described in the disclosure of the PCT Publication No. WO 2006/110917, the entire disclosure of which is incorporated herein by reference. From some sources, ·> 143924-SD-20091127-1 - 155- 201020257 For example, Sigma Aldrich, Lancaster Synthesis, Maybridge, Matrix Scientific, T CI and Fluorochem USA, etc., or synthetically based on sources known to those skilled in the art (see, for example, Smith, MB and J. March, High #岁讥允学.· and shoulders, socks and pants, 5th edition) (Wiley, December 2000)), or may be made as described in the PCT published patent application WO 2006A10917, or may be made by the methods disclosed herein. The protecting group may be added or removed according to standard techniques. It is known to those skilled in the art and as described herein. The use of protecting groups is described in detail in Greene, T.W. and P.G.M. Wuts, Oeene Martial Protection (2006), 4th edition, Wiley. The protecting group may also be a polymer resin such as Wang resin or gasified 2-a gas-based benzotriene resin. It will also be apparent to those skilled in the art that while such protected derivatives of the compounds of the invention may not themselves have pharmacological activity, they may be administered to a mammal and subsequently metabolized in the body to form a pharmacological agent. A compound of the invention that is active. Such derivatives may thus be described as "prodrugs". All prodrugs of the compounds of the invention are included within the scope of the invention. All of the compounds described below, when prepared, may be in the form of a free base or acid which may be converted to a pharmaceutically acceptable salt thereof by treatment with a suitable inorganic or organic base or acid. Salts of the compounds prepared below can be converted to their free base or acid form by standard techniques. It is to be understood that all polymorphs, amorphous forms, anhydrates, hydrates, solvates and salts of the compounds of the invention are intended to be within the scope of the invention. Furthermore, all of the compounds of the invention containing 143924-SP-20091127-1 -156. 201020257 oxime or ester groups can be individually converted into their corresponding ones by methods known to those skilled in the art or by the methods described herein. Ester or acid. Alternatively, the compounds of the invention may be synthesized according to the procedures described below in Schemes 1-27, wherein unless otherwise indicated, q is 1 or 2, and each X is a halo group, preferably a molybdenum or a gas group. , R, is an alkyl group, and Rl5 is as defined in Formula 1, Formula (II), Formula (III), Formula (IV), Formula (v), Formula (VI), Formula (10), Formula (10), Formula (vm) ), R (R), Rb, R3, R5, R7, R9, R1, R5, R7

It is defined by r2, r4 or R6 in the compounds of formula (I), formula (II) and formula (III), and is defined as one of the following:

Wherein, 艮1^, %, 1;, 乂%丫 and 2 are as defined in relation to formula (1), formula (111), formula (乂1), formula (VII), formula (VIII), formula (IX) , formula (XI) and formula (ΧΙΠ) compounds. Preparation of Compounds of Formula (la), Formula (Iaa) and Formula (lab) The compounds of formula (la), formula (Iaa) and formula (lab) are the compounds of the invention as set forth above in the Summary of the Invention. It can be produced by the method proposed in the following Reaction Schemes 1 and 2, wherein R5〇a, 圮(10), R5〇c&R5〇d are each independently hydrogen, meridional, molybdenum, gas-based, Cyano, I, methyl, triwattyl, decyloxy, 1-mercaptoethoxy, 2-methoxyethoxy, fluorenyl, i (tris-butoxy) Tetrahydropyrrol-3-yloxy, tetrahydropyrrolidinyloxy, amine, 143924-sp-20091127-1 -157· 201020257 Continuation of mercaptoamine, methanesulfonylamino, [(third_ Butoxycarbonyl)tetrahydropyrrole-3-yl]amino, 6-methoxypyridin-3-yl, 5-methyl-1,2,4-oxadiazol-3-yl, amine (hydroxyimine) Methyl or (tetrahydropyrrole-3-yl)amine; or hydrazine (^ and 115()1), or R5〇i^R5()e ', together with the adjacent carbon to which they are attached Fused dioxoenyl ring, fused pyrimenyl ring, fused U-diketopyrimenyl ring, fused u, 5_p oxadiazole ring, thickened a tetrahydro-hydrocarbyl ring, a fused 2,3-dihydro-7-base ring, slightly conjugated: a methyl-4,5-dihydroisocyclic ring or a fused μ-based ring 1 R5〇b, R5〇1R5 d 'If present, the system as described above: ,,

(r'-CQ reaction pattern (R, 6) q4

143924-SP-20091127-1 -158- 201020257 Compounds of formula (101), formula (102), formula (104), formula (105), formula (110) and formula (112) are commercially available or may be It is made according to methods known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in PCT Publication No. WO 2006/110917. As set forth above, the compound of the formula (la) is produced by first alkylating a compound of the formula (101) with a gas group of the formula (102) or a bromine compound to obtain a product of the formula (103). Alternatively, the compound of formula (110) is iodinated with iodine and alkylated with a gas group or a bromine compound of formula (102) to give the product of formula (111). Ο (111) is obtained by gasification of ruthenium (III) monohydrate with sodium periodate to obtain a product of formula (103). Alternatively, the aniline compound of the formula (112) is treated with gasified grass mash to obtain a ruthenium compound of the formula (103). The phenol compound of the formula (104) is treated with a Grignard reagent of the formula (105) at a low temperature (0 ° C) to form a phenoxy magnesium halide intermediate to form a ketone with the oxime compound of the formula (103) (9). The carbonyl group is reacted in a solvent such as, but not limited to, dichloromethane or tetrahydrofuran to give the oxime of the formula (106). The compound of formula (107) is obtained by treating a compound of formula W (106) with a decane such as, but not limited to, triethyl decane after removal of the hydroxy group at the C-3 position of the fluorenone. The compound of the formula (107) can also be obtained by treating the compound of the formula (106) with thionous sulphide/triethylamine and then reducing it by pulverization. The compound of formula (107) is an alkylating agent such as, but not limited to, chloromethyl iodide or 1,2-dibromoethane, using a base such as, but not limited to, a carbonic acid planing agent such as, but not limited to, tetrahydrofuran. Or treatment with N,N-dimercaptocaramine to obtain a compound of the formula (la) of the present invention via intramolecular cyclization. Alternatively, compound (107) is treated with a decyl compound such as, but not limited to, trimethyl decane chloride to produce a decyl ether intermediate which is mirrored with trifluorosulfonate (III) 143924-sp-20091127 -1 -159- 201020257 The compound of formula (108) is obtained by treatment with formaldehyde. The compound of the formula (108) can also be obtained by treating a compound of the formula (107) with a base such as, but not limited to, LiOH, iPr2NH, LDA, and then reacting with a hydrazine. a compound of formula (108) via a Mitsunobu reaction in the presence of a phosphine reagent such as, but not limited to, triphenylphosphine, tributylphosphine or trimethylphosphine, and diethyl, diisopropyl or di-tertiary-butyl nitrogen Intramolecular cyclization of a dicarboxylate or hydrazine, hydrazine, hydrazine, Ν'-tetradecylazodicarboxyguanamine in a solvent such as, but not limited to, tetrahydrofuran, ethyl acetate or dichloromethane, The compound of the formula (la) of the present invention is obtained. The compounds of the formula (la), (Iaa) and (lab) can also be produced by the method shown in the following Reaction Scheme 2, wherein 屮1115, ruler 16,115()3,115()1\foot 5() . And 115() (1 are as defined above, and PG is a nitrogen protecting group: reaction pattern 2

Compounds of formula (203), formula (204), formula (205), formula (206), and formula (207) are commercially available or may be according to methods known to those skilled in the art or as disclosed herein. Method preparation. A compound of the formula (201) wherein PG is a nitrogen protecting group such as, but not limited to, diphenyl 143924-sp-20091127-1 -160-201020257. The methyl group is synthesized in the order shown in the above Reaction Scheme 1. When the protecting group is a diphenylmethyl group, it is removed under a high pressure of hydrogen, such as 60120 PS1, to form a decyl ketone compound of the formula (202); it can also be obtained by a compound of the formula (2〇1) Diethyl zebra and trifluoroacetic acid at 7 Torr. It is removed and processed. The formation of a compound of formula (la) is achieved by alkylation of a compound of formula (202) with an alkylating agent R15-X (203) wherein X is chloro, bromo, iodo or OTs, or When X is a gas group, the reagent is produced from its corresponding alcohol (204)' in a manner compatible with a gasification reagent such as, but not limited to, sulfur dichloride or chlorination (chlorobenzylidene) Indoleamine salt (Vilsmeier reagent)), in the presence of a base such as, but not limited to, sodium hydride, sodium bis(trimethyldecyl)amine, hydrazine hydroxide or carbonic acid, in a solvent such as, but not limited to, N, N A combination of dimethylformamide, tetrahydrofuran, 2-butanone, acetone, acetonitrile or any combination of the two is reacted in the presence or absence of potassium iodide. Alternatively, a compound of formula (202) and an alcohol (204), under Mitsimobu reaction conditions, in the presence of a phosphine reagent such as, but not limited to, triphenylphosphine, tributylphosphine or trimethylphosphine, and diethyl, diisopropyl , di-t-butyl butyl dicarboxylate or hydrazine, hydrazine, hydrazine, Ν--tetramethylazodicarbamoylamine, in a solvent such as, but not limited to, tetrahydrofuran, ethyl acetate or dichloro The reaction in decane provides a compound of the formula. Alternatively, a compound of the formula (202) and dihydroxyborane (2〇5) in a copper reagent such as, but not limited to, copper acetate and 4-(N,N-dimethylamino)>pyridinium, a base such as but not limited to six The reaction of a solvent such as, but not limited to, toluene in the presence of sodium sulfonate is provided as a compound of the formula (la). Alternatively, when the RU in the compound (203) is an aryl or heteroaryl group, Compound (203) is combined with compound (202) in a palladium catalyst such as, but not limited to, palladium acetate 143924-sp-20091127-1 .161 . 201020257 (II), such as but not limited to 9,9-dimethyl -4,5-bis(diphenylphosphino)dibenzopyran' and a base such as, but not limited to, a carbonic acid planer, reacted in a solvent such as, but not limited to, 1,4-dioxane, to provide (Ia) product. Generally, the compound of the formula (202) is a base such as, but not limited to, sodium hydride or diethylamine, and a gas sulphuric acid, such as, but not limited to, sulphuric acid or dicarbonic acid. The treatment of di-tertiary-butyl ester provides a compound (Iaa) amino phthalate compound. The compound of formula (202) is treated with a hydrating reagent such as, but not limited to, acetic acid liver. Preparation of the formula (LB) of the compound of compound of formula (LB) and formula (Ic) provides formula (Lab) and (Ic) is a compound of the invention as hereinbefore set forth in the Summary of the Invention

The compound j can be prepared by the method proposed in the following Reaction Scheme 3, wherein (G)N is a N. heterocyclic group, PG is a nitrogen protecting group, and q and R1 6 and © are as defined above. R17 and RU are each independently hydrogen or alkyl, and Rlg is hydrogen, alkyl or aryl: 143924-sp-20091127-1 162- 201020257

Reaction pattern 3

The compound of formula (301) can be prepared according to methods known to those skilled in the art, or by methods not disclosed herein, or by the method disclosed in PCT Publication No. WO 2006/110917. The compounds of formula (10) and formula (10) are commercially available or can be prepared according to methods known to those skilled in the art. Typically, the compound of formula (lb) and formula (Ic) is prepared by the procedure set forth above in Reaction Scheme 3, in the following manner, and the compound is removed using a method known to those skilled in the art. To produce the formula _ compound. _ or _ (303), in a reducing agent, such as but not limited to sodium borohydride or sodium triethoxy borohydride, or, with furfural and formic acid, reductive amination in reflux water, An amine compound of formula (Ic) is provided. In another aspect, the urea compound of formula (lb) is obtained by reacting an amine compound of formula (3〇2) with an isocyanate in the presence of a base such as, but not limited to, triethylamine or diisopropylethylamine. However, it is not limited to the treatment of two gas methane or gas imitation to make 143924-SP-20091127-1 -163- 201020257. Preparation of the compound of formula (Id) The compound of formula (10) is a compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth in Reaction Scheme 4, wherein the aryl group (wherein -CN is a substituent on the aryl group of the aryl group or on the heteroaryl group of the heteroaryl group), And R2G is hydrogen, alkyl, i-based or ring-based: reaction pattern 4

The compound of the formula (401) can be obtained according to a method known to those skilled in the art, or by the present

The method disclosed in the text, or by the method disclosed in the PCT Published Patent Application No. 2006/110917. Reaction Scheme 4 illustrates the formula (Id) No. 2. Summary synthesis of base compounds. The compound of the formula (402) can be obtained by treating a compound of the formula (4〇1) with an amine in a solvent such as, but not limited to, disulfoxide. The compound of the formula (4〇2) is obtained by using an anhydride or gasified hydrazine substituted with 143924-sp-20091127-1 -164- 201020257, in the presence of a base, such as but not limited to pyridine (also as a solvent) In the microwave reactor, it is at a high temperature such as 17 Torr. The reaction is subsided and converted to the compound of formula (id). Alternatively, the oxadiazole ring is formed by passing the δ (402) with an appropriately substituted anhydride or gasification in the presence of, for example, but not limited to, diisopropylamine, in a solvent such as, but not limited to, two. It is achieved by reaction in methyl chloride. Alternatively, the compound of formula (402) may be reacted with an appropriately substituted gasified hydrazine in the presence of a base such as, but not limited to, diisopropylamine, in a solvent such as, but not limited to, a hydrazine to cause a formula ( 4〇3) Formation of the compound, which is then treated with a base such as, but not limited to, pyridine (also as a solvent) in a microwave reactor at a temperature of, for example, 170 ° C to provide a compound of the formula. Preparation of the compound of the formula (le) and the formula (H) The compound of the formula (Ie) and the formula (if) is a compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth in Reaction Scheme 5 below, wherein q, R16 and D are each as defined above, which is an N-heteroaryl group, and φ R21 and R22 are each independently hydrogen, alkyl, An aralkyl or aryl group, or R2!, together with the nitrogen to which they are attached, forms an optionally substituted oxime-heteroaryl or fluoren-heterocyclyl: 143924-sp-20091127-1 • 165· 201020257 Reaction pattern 5

~/7, Dian Jingtian, the method disclosed in the article, 岑 A A DPT \ 1 ^ is made by the method disclosed in the PCT application patent application w〇 2〇〇6/110917. In general, the above reaction scheme 5 illustrates a schematic synthesis of the compound of the formula (10) and the formula (If). The compound of the formula (10) is obtained by combining the formula 16 with an amine, such as, but not limited to, dimethylamine, hexahydro- or a solvent, in a solvent, the chain is not limited to the Gu-f-methyl group (IV), at a high temperature. For example, it is obtained by processing under the boot. In another aspect, the compound of the formula (10) is nucleophilic with an oxide, such as, but not limited to, sodium methoxide, in a solvent, such as a N,N-dimethylformamide, The high temperature dish f is obtained by treatment at 120C. Preparation of the compound of the formula (Ig) The compound of the formula (Ig) is the present invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth in Reaction Scheme 6 below, and is defined as above in the above-mentioned 143924-sp-20091127-l 166 201020257, and Q is a stretching bond, an aryl group or a heteroaryl group ( Wherein the side (10)" is a substituent on the aryl group of the aryl group or on the heteroaryl group of the heteroaryl group, R23 is an alkyl group, and the r24 and r25 groups are each independently hydrogen, an alkyl group, a cycloalkyl group. , aryl or heteroaryl;

Reaction pattern 6

Compounds of formula (601) can be prepared according to methods known to those skilled in the art, or by methods disclosed herein, or by the methods disclosed in the PCT Publication No. WO 6 601/110917. Slave 5 'Reaction Scheme 6 is a schematic synthesis of a compound of formula (ig). The ester compound of formula (601) is converted to its corresponding formula (6〇2) by acid, by ester of formula (601). The compound 'is treated, for example, but not limited to, a hydrazine hydroxide, sodium hydroxide or potassium hydroxide, in a mixed solvent such as, but not limited to, tetrahydrofurfuryl or decyl alcohol and water. The acid compound of formula (602) can be converted to a mixed anhydride by treatment with isobutyl chloroantimonate in the presence of a base such as, but not limited to, N-methylmorpholine or its corresponding turbidity. In the presence of a catalytic amount of N,N-dimercaptodecylamine in a solvent such as, but not limited to, toluene, di-methane or gas, in the presence of a gasification grass, 143924-sp-20091127-1 -167- 201020257 deal with. The mixed anhydride is directly reacted with the following, or the vaporized lanthanide is reacted with, in the presence of a base, such as but not limited to diethylamine or monoisopropylethylamine, a primary or secondary amine, to form a brewing amine compound. (603). When R24 and R25 are each hydrogen, the compound of formula (6〇3) is combined with n,N-mercaptoacetamide dimethyl hydrazine in a solvent such as, but not limited to, 1,4-dioxane. The reaction 'produces an intermediate which reacts with hydrazine to form a (Ig) tri-beta compound. Formula (Ih), Formula (Ii), Formula (Ka), Formula (Iib), Formula (Iic), Formula (1), Formula (called, Formula (Ika), Formula (Ikb), Formula (Ike), Formula (I) Preparation formula of formula Ikd), formula (Ike) and formula (Ikf), formula (Ii), formula (Iia), formula (lib), formula (Iic), formula (cut, formula (Ik), formula ( Ika), formula (Μ»), formula (Ike), formula (Ikd), formula (ike) and formula_compound are the compounds of the invention as set forth above in the Summary of the Invention, which can be used in the reaction scheme below Made by the methods set forth in 7 and 8, wherein q, Ri5, Rl gr and D are as defined above, (〇 is aryl or heteroaryl, Μ6, r27 and R are each independently hydrogen 'burning, view a substituted aryl or optionally substituted heteroaryl, and R35 is alkyl, aryl or heteroaryl: 143924-SP-20091127-1 •168· 201020257 Reaction Scheme 7

201020257 Reaction pattern 8

The compounds of formula (701) and formula (801) can be used as known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in PCT Publication No. WO 2006/110917. production. In general, the formula (Ih), the formula (Ii), the formula (Iia), the formula (Iib), the formula (Iic) ', that is, the formula (Ik), the formula (Ika), the formula (Ikb), the formula (Ike) The compounds of the formula (ikd), formula (Ike) and formula (Ikf) are synthesized as shown in Reaction Scheme 7 or Reaction Scheme 8. A compound of the formula (7〇1) or (801) is a primary or secondary amine in the presence of a catalyst such as, but not limited to, palladium acetate, ruthenium (triphenylphosphine) palladium (0) or bis(diphenylene). Methyl acetonide) genomic (〇) with or without ligands such as, but not limited to, triphenylphosphine, tri (o-143924.sp.20091127.1 -170· 201020257 -tolyl)phosphine, 1, bismuth-double ( Diphenylphosphino)dicyclopentadienyl iron or 2-(di-tertiary-butylphosphino)biphenyl 'test' such as but not limited to sodium carbonate, carbonic acid planing or sodium tributoxide, in solvents such as However, it is not limited to the reaction of indole, dioxere or tetrahydrogen to provide an amine compound of formula (Iia) or formula (Ika) (see Muci, AR et al., Deutero/6 # test (2002) , 219 : 131). Or a compound of the formula (701) or (801) and a cyclized endoamine of the compound, in a copper catalyst such as, but not limited to, copper molybdenum (I), such as but not limited to 8-hydroxyl Set of u or racemic-trans-N,N,-dimercaptocyclohexan-1,2-diamine, eg, in the presence of, but not limited to, potassium carbonate in a solvent such as, but not limited to, dimethyl The reaction in a sulfone provides a product of formula (Iia) or formula (Ika). Alternatively, the carboxylic acid compound of the formula (702) and the diphenyl azide are obtained in the presence of an amine such as, but not limited to, triethylamine and a third butanol, reacted in a solvent such as, but not limited to, toluene to obtain a third - A butoxycarbonyl protected amine-based intermediate which, upon acid treatment, results in the formation of an amine-based compound of formula (Iia) wherein each of R26 and R27 is hydrogen. The compound (701) or (8〇1) is bonded to an alkyl, vinyl, aryl or heteroaryl diradonic or alkyl, vinyl, aryl or heteroarylstannane reagent. In the presence of a medium such as but not limited to palladium acetate, ruthenium (triphenylphosphine) palladium (9), ginseng (diphenylmethyleneacetone) dipalladium (9), with or without ligands such as, but not limited to, triphenylphosphine, three (o-tolyl)phosphine, U,-bis(diphenylphosphino)dicyclopentadienyl iron or 2-(di-tert-butylphosphino), stigma, base, such as but not limited to sodium carbonate , cesium carbonate or sodium bicarbonate, reacted in a solvent such as, but not limited to, dioxetane, dioxane or tetrahydrofuran to provide a formula (ie, or as a coupled product (see Kotha, S. et al., and (2002), 58: 9633, and 143924-sp-20091127-1 -171· 201020257

Miyaura, N. et al., C/zem. (1995), 95: 2457, and Farina, V. et al., (1997), 50: 1). The compound (701) or (801) is combined with sodium cyanide, zinc cyanide or tributyltin cyanide and potassium cyanide in a nickel catalyst such as, but not limited to, vaporized nickel (II), or a palladium catalyst such as but not limited to Palladium acetate, stilbene (diphenylmethyleneacetone) dipalladium (9), and ligands such as, but not limited to, tris(o-tolyl)phosphine, 1, bismuth-bis(diphenylphosphino)dicyclopentadiene In the presence of iron or 2-(di-t-butylphosphino)biphenyl, it is reacted in a solvent such as, but not limited to, hydrazine, hydrazine-dimethyl decylamine, 1-decyltetrahydropyrrolidone or acetonitrile. To provide a cyano compound of formula (Ii) or formula (Ik) (see Marcantonio, Κ.Μ. © et al, Org. Leit (2004), 6: 3723-5, and Yang, C. et al., Og. Lett (2004), 6 : 2837-40). Compound (701) is with sodium sulfonate, such as but not limited to sodium decane sulfonate, in the presence of a copper catalyst such as, but not limited to, copper iodide, in the presence of a sodium salt of L-valine, in a solvent such as, but not limited to, The reaction is carried out in a diterpenoid to provide a product of the formula (lib). In the compound of the formula (Ika), when each of R26 and R27 is hydrogen, it is coupled with a carboxylic acid, and is carried out by a person skilled in the art to provide a guanamine compound of the formula (Ikb). Alternatively, the amine compound of formula (Ika) is treated with an amine in the presence of a coupling agent such as, but not limited to, trimethyl gas phthalate to provide a urea compound of formula (Ike). Compound (801) is an alcohol and carbon monoxide in a palladium catalyst such as, but not limited to, palladium acetate, and a ligand such as, but not limited to, 1,3-bis(dicyclohexylscale)propane bis(tetrafluoroborate), and The reaction of a base such as, but not limited to, potassium carbonate in a solvent such as, but not limited to, N,N-dimethylformamide to provide an ester compound of formula (Ij) wherein R28 is -COOR25 (wherein R25 is as defined above) ). When R25 143924-sp-20091127-1 -172-

(SJ 201020257 is a phenyl group. The compound of the formula is treated with an amine in the presence of a base such as, but not limited to, potassium carbonate in a solvent such as, but not limited to, n, n-dimethylmethanamine. _ 醯 化合物 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 。 This is a formula (Ikd)-grade guanamine compound. The formula (Ikd)-grade guanamine compound is obtained by hydrolysis of a sodium carbonate aqueous solution and hydrogen peroxide in a solvent such as, but not limited to, ethanol. Alternatively, a compound of the formula can be obtained by treating a compound of the formula (Ik) with an amine in a solvent such as, but not limited to, a dimethyl sub-unit. The compound is hydrolyzed by appropriately substituted liver or chlorination. In the presence of, for example, but not limited to, pyridine (also as a solvent), it is converted to a compound of the formula in a microwave reactor at a high temperature, such as 17 ° C. Alternatively, when the rule 27 is hydrogen. , formula (Iia) and a) compound system and gasification sulfonium reagent For example, but not limited to, chlorinated methane sulfonate, in the presence of a base, such as but not limited to a bite, reacted in a solvent such as, but not limited to, a gas or a chloroform to provide a formula (lie) and ((10) indeed brewed Amine product. Preparation of a compound of formula (Im) and formula (Ima) The compound of formula (Im) is a compound of the invention as set forth above in the Summary of the Invention, which can be prepared by the method set forth below in Scheme 9 Cheng, where 屮1115,1116, 尺2〇, 1^6 and 1127 are as above: 143924兮20091127-1 •173· 201020257 Reaction pattern 9

Compounds of formula (901) can be prepared according to methods known to those skilled in the art, or by methods disclosed herein, or by the methods disclosed in PCT Publication No. 2006/110917. In general, the compounds of the formula (Im) and the formula (lma) are synthesized as shown in Reaction Scheme 9. The compound of the formula (901) is a primary or secondary amine in the presence of a saturated catalyst such as, but not limited to, palladium acetate (11), ruthenium (triphenylphosphine), (9) or ginseng (diphenylmethyleneacetone) dipalladium. (0), with or without a ligand such as, but not limited to, triphenylphosphine, tris(o-tolyl)phosphine, 1,1,-bis(diphenylphosphino)dicyclopentadienyl iron or 2_ (di-t-butylphosphino)biphenyl, a base such as, but not limited to, sodium carbonate, carbonic acid planing or sodium tributoxide, reacted in a solvent such as, but not limited to, toluene, dioxane or tetrahydrofuran, To provide an amine compound of the formula (Im) (see MuciAR et al., 涴/C /6 school age (2〇〇2), 219: 131). The compound (9〇1) is combined with sodium cyanide, zinc cyanide or tributyltin cyanide and potassium cyanide in a nickel catalyst such as, but not limited to, vaporized nickel (11), or a palladium catalyst such as but not 143924-sp -20091127-1 •174· 201020257 is limited to palladium acetate, bis(diphenylarbenium acetonide) dipalladium (ο), and ligands such as, but not limited to, tris(o-tolyl)phosphine, l,r-double ( In the presence of diphenylphosphino)dicyclopentadienyl iron or 2-(di-tertiary-butylphosphino)biphenyl, in a solvent such as, but not limited to, hydrazine, hydrazine-dimethylformamide, 1- Reaction with methyltetrahydropyrrolidone or acetonitrile to provide a cyano compound of formula (902) (see Marcantonio, Κ.Μ. et al, Leii. (2004), 6: 3723-5' and Yang, C. et al. , Og. L. (2004), 6: 2837-40). The compound of the formula (902) is brewed with hydroxylamine, and with an appropriately substituted anhydride or gasification, in the presence of a base such as, but not limited to, pyridine (also as a solvent) in a micro-parameter reactor. Treatment at 170 ° C to provide the product of the formula (ima). Preparation of compounds of formula (In) and (Ina) wherein R15, R26, R27 and ® alkyl, hydroxyalkyl or decyl: compounds of formula (In) and (Ina) are as hereinbefore described in the Summary The compounds of the invention are presented. It can be as defined above by the method proposed in the reaction scheme 1 ’ below and R29 is _C(〇)H, reaction pattern 10

201020257 Formulas can be made according to the methods disclosed in the methods known to those skilled in the art, or by the method disclosed in PCT Publication No. 2006/110917. System independence

In general, the compound of the formula (In) can be as shown in the reaction scheme 1 ,, with a clock reagent such as, but not limited to, n-butyl J or: _ butyl lithium, in a solvent such as, but not limited to, tetrahydrofuran Or treatment in diethyl ether produces an anion which is reacted with an electrophile to provide a compound of formula (9). When the electrophile is N,N_:f-based decylamine, the aldehyde compound of the formula (1002) wherein r C(0)H is obtained is obtained from the amine, under reductive amination conditions, such as a reducing agent. The reaction is carried out in the presence of sodium cyanide or sodium triethylate (tetra) to provide an amine compound of formula (h). Alternatively, a compound of formula (1001), in the form of an alcohol, such as, but not limited to, a diol, a phenol or a substituted aryl group and a heteroaryl group-based compound, in a copper reagent such as, but not limited to, copper (I) iodide, a ligand For example, but not limited to 3,4,7,8_tetramethyl-丨, melon ii phenanthrene, and test, such as but not limited to carbon (10), in the solvent, such as but in toluene, provide the formula (Ina ) an ether compound. Alternatively, the compound of the formula (1001) is treated with a lithium reagent such as n-butyllithium or a second butyllithium, a boron reagent such as, but not limited to, tridecyl borate, followed by oxidation with hydrogen peroxide. (1003) a hydroxy compound. Formula (10)) Sigma, aryl or heteroaryl, in copper reagents such as, but not limited to, copper (I) iodide, ligands such as, but not limited to, μ butyl 1 imidazole and alkali such as but not An ether compound of the formula (Ina) is provided in the presence of potassium carbonate in the presence of a solvent such as, but not limited to, toluene. Alternatively, a compound of formula (1003) is treated with a base such as, but not limited to, cesium carbonate in 143924-SP-2009 H27.1 -176 - 201020257 solvent such as, but not limited to, N,N-dimethylformamide, and with a tooth The reaction of the base reagent R27-X gives an ether compound of the formula (Ina). Preparation of a compound of the formula (1〇) The compound of the formula (1〇) is a compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth below in Reaction Scheme η, wherein ... and R" are as defined above, and r30 is alkyl, cycloalkyl or heterocyclyl:

Reaction pattern 11

(1101) η

R30~〇H or ” R30-X

The compound of formula (1101) can be prepared according to methods known to those skilled in the art, or by the methods disclosed in the present invention, or by the method disclosed in PCT Publication No. 2006/110917. In general, the reaction scheme U is a schematic synthesis of a compound of the formula (1). The benzyl protecting group of (1101) is selectively removed by hydrogenation in a solvent such as, but not limited to, a fermentation, under a pressure of one atmosphere of hydrogen, with a catalyst such as, but not limited to, neo/carbon. To provide a compound of formula (10) 2). Formula (compound with alcohol (R3 0 · 〇Η), at Mitsunnhl1 g, from % Mitsunobu reaction conditions, under phosphine reagent 143924-sp-20091127-1 201020257, such as but not limited to triphenylphosphine, tributyl Phosphine or trimethylphosphine, and diethyl, diisopropyl, di-tertiary-butyl nitrogen dicarboxylic acid vinegar or N, N, N, N, tetramethylazo-retamine, The solvent is reacted, for example, but not limited to, tetrahydrop-pentane, ethyl acetate or dichloromethane to provide a compound of the formula (1). Alternatively, the compound of the formula (1102) may be a base such as, but not limited to, potassium carbonate or hydrogenated. Sodium, which is treated in a solvent such as, but not limited to, N,N-dimethylformamide or tetrahydrofuran, and reacted with an alkyl halide, r3〇_x, provides a compound of formula (1〇). The compound of the formula (Ip) is prepared according to the invention as set forth above in the Summary of the Invention, which can be prepared by the method set forth below in Reaction Scheme 12, wherein R'q'R15 and R16 are as above.定彡' and r31 is alkyl or haloalkyl: Reaction Scheme 12

The compound of formula (1201) can be prepared according to methods known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in the PCT Patent Publication No. W〇2〇〇6/110917 to make. Formula (1〇5) compound (4) is commercially available. General, p, reaction scheme 12 is a schematic synthesis of a compound of formula (ip). An alcohol compound of the formula (1201), which is treated at a low temperature (叱), to form a phenoxy magnesium halide intermediate, which is an electrophilic agent such as, but not limited to, trifluoroacetic anhydride. The compound of the formula (ip) is obtained by reacting in a solvent such as, but not limited to, dioxane methane 143924-sp-20091127-1 •178-201020257 or tetrahydrofuran. Preparation of Compounds of Formula (Iq), Formula (Ir) and Formula (Is) The compounds of formula (Iq), formula (Ir) and formula (Is) are the compounds of the invention as set forth above in the Summary of the Invention. It can be made by the method set forth below in Reaction Scheme 13, wherein ^16, Ruler 26, 圮7 and © are as defined above, and you are. - alkyl group, R32 is hydrogen or alkyl, and R33 is hydrogen, alkyl, _alkyl, cycloalkyl or heterocyclic: Reaction Scheme 13

The compound of formula (1301) can be made according to methods known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in the patent application of WO Pers. . Compound r33_x is commercially available. In general, the reaction scheme 13 is a schematic synthesis of a compound of the formula (Iq), the formula (Ir) and the formula (Is). The oxygen protecting group in the compound of formula (1301) is removed by the method known to those skilled in the art to provide an alcohol compound of formula (13〇2). Using a reagent (bromo, gas or bromo) reagent (R33_X) in the presence of a base such as, but not limited to, cesium carbonate, sodium hydride or potassium carbonate in a solvent such as, but not limited to, tetrahydrofuran or N, N - alkylation in dimethylformamide, 143924-SP-20091127-1 -179-201020257 for the compound of formula (Iq). When R3 2 in the compound of the formula (1302) is hydrogen, the -first alcohol is oxidized by an oxidizing agent such as, but not limited to, 1,1,1-glycol (ethoxy)oxyl-1,2-benzoin Oxime _3-(ih)-ketone (Dess-Martin over-cracking) is oxidized to form its corresponding aldehyde compound of formula (1304), which is linked to an amine, under reductive amination conditions, such as but not The reaction is limited to the presence of sodium cyanoborohydride or sodium triethoxysulfonate to provide an amine compound of formula (!r). In another aspect, the compound of formula (1304) is reacted with a nucleophilic agent, such as, but not limited to, a combination of methyl bromide or difluoromethyl dimethyl methane and a fluorinated planer to form a formula. Compound. Preparation of the compound of the formula (10) The compound of the formula (8) is a compound of the invention as set forth above in the Summary of the Invention. It can be produced by the method set forth below in Reaction Scheme 14, wherein q' R16 and D are both as defined above and C3 is an optionally substituted N-heterocyclic group:

Reaction pattern 14

The compound of formula (1401) can be prepared according to methods known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in the PCT Publication No. 110917. In general, Scheme 14 illustrates the schematic synthesis of a compound of formula (8). The compound (1.) of the compound 'in the case of the optionally substituted n-heterocyclic group is present in 143924-sp-20091127-l-180- (201020257 under 'such as but not limited to 4_mercaptohexahydropyrazine or hexahydro Pyridine, treatment in a solvent such as, but not limited to, methanol, provides a compound of formula (8). Preparation of a compound of formula (Iu) The compound of formula (Iu) is a compound of the invention as set forth above in the Summary of the Invention. The following is prepared in the method set forth in Reaction Scheme 15, wherein X, q, Ri6 and 1^) are as defined above, and © £^nh ^ ^ L ^ ^ ^ " 〇 is replaced as appropriate

N-heteroaryl or optionally substituted N-heterocyclyl, and R34 is alkyl or —alkyl: earth s-square Reaction Scheme 15

The compound of formula (10) can be used according to methods known to those skilled in the art, or by the methods disclosed herein or by the patent application filed by the PCT.

Made by the method not disclosed in 110917. Compound r3 [x is commercially available. General P Reaction Scheme 15 illustrates the general synthesis of the compound of formula (Iu). a compound of formula (1501), such as, but not limited to, sodium hydride and a crystallization reagent (R34-X)' in a solvent such as, but not limited to, tetrahydrofuran or n,n-dimethylamine A compound of formula (10) is provided. Alternatively, the alkylation is carried out by reacting a compound of the formula (10) D with an alkylating agent such as but not (iv) dimethyl sulphate under phase transfer reaction conditions such as, but not limited to, sodium oxyhydroxide, a phase transfer catalyst. For example, but not limited to, tetrabutylammonium bromide, is achieved by reaction in a solvent of 譬-181 · 143924-sp-20091127-1 201020257, such as but not limited to aqueous tetrahydrofuran, to provide a compound of formula (Iu). Preparation of compounds of formula (Iv) and (Iva)

The compounds of formula (Iv) and (Iva) are the compounds of the invention as set forth above in the Summary of the Invention. It can be made by the method set forth below in Reaction Scheme 16 wherein r15, r20 and are as defined above: Reaction Scheme 16

The formula (1601) can be made according to the method known to those skilled in the art, or by the method disclosed in the present invention, or by the method disclosed in the PCT Publication No. WO 2006/110917. As usual, §, reaction 囷 16 is an outline of the compounds of formula (Iv) and (Iva) 4 ° 4 _ ^ | things 'with vinyl ether' such as but not limited to butyl vinyl, in the media such as but not Limited to (four) peaks, ligands such as, but not limited to, 1,3-bis(diphenylphosphino)propene&, and such as, but not limited to, the presence of carbonic acid in the presence of a solvent such as, but not limited to, w-dimethyl Treatment with guanamine provides a compound of formula (10) 2). (10) 2) A bromine-based compound of the formula (1603) is obtained by bromine 143924-sp-20091127-l • 182·201020257 of tri-pure phenyltrimethylammonium. (1603) A reaction with a sulfur-containing reagent such as, but not limited to, thioacetamide or thiourea to obtain a pyrimide compound of the formula (Iv). Alternatively, (1602) is treated with a strong, for example, but not limited to, sodium nitride, followed by a reaction with diethyl carbonate in a solvent such as, but not limited to, tetrahydrofuran to obtain a dicarboxy compound of formula (1604). Cyclization to provide a pyriva compound of formula (lva). Preparation of the compound of the formula (Iw) The compound of the formula (Iw) is a Φ compound of the invention as set forth above in the Summary of the Invention. It can be produced by the method set forth below in Reaction Scheme 17, (g〇n (T) ^ wherein q, R16 and ^ are as defined above, and NH2 is optionally substituted N-heteroaryl :

Reaction pattern 17

Compounds of formula (1701) can be prepared according to methods known to those skilled in the art, or by methods disclosed herein, or by the methods disclosed in PCT Publication No. WO 2006/110917. In general, Scheme 17 illustrates the schematic synthesis of a compound of formula (Iw). The compound of the formula (1701) is treated with N,N-dimercaptoguanamine fluorenyl acetal to obtain a ruthenium imine compound of the formula (1702), which is in the form of a trifluoroacetic anhydride, for example but When not limited to treatment in tetrahydrofuran, it provides a compound of the formula (Iw) cyclized. 143924-SP-20091127-1 -183-201020257 Preparation of the compound of the formula (lx) The compound of the formula (lx) is a compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth below in Reaction Scheme 18, wherein q and 尺 16 and © are as defined above, Qb is an alkyl or aralkyl group, and R35 is an alkyl group, an aryl group or Heteroaryl:

Reaction pattern 18

The compound of the formula (1801) can be prepared according to methods known to those skilled in the art, or by the methods disclosed in the present invention, or by the method disclosed in the PCT Publication No. WO 06/110917. In general, Scheme 18 is a schematic synthesis of a compound of formula (ι). The compound of the formula (1801) is treated with hydrazine to obtain an amine compound of the formula (10) 〇 2) which, when reacted with a deuteration reagent, is provided by the formula, to provide a decylamine compound of the formula (lx). Preparation of a compound of formula (iy) The compound of formula (iy) is a compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth below in Reaction Scheme 19, wherein q, R16 and @ are as defined above, and Q is an alkylene chain, an aralkyl group, an aryl group or a heteroaryl group (where - CONH2 is a substituent on the aryl group of the aralkyl group and on the heteroaryl group of the heteroarylalkyl group), and R35 is an alkyl group, an aryl group or a heteroaryl group: 143924-sp-20093127-1 •184- 201020257 Reaction pattern 19

The compounds of the formulae (1901) and (1902) can be used according to methods known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in PCT Publication No. WO 2 6/110917. production.

In general, 'reaction scheme 19' is a schematic synthesis of a compound of formula (Iy). The compound of formula (1901) is treated with a urethane, such as, but not limited to, dimethylacetamide dimethyl acetal, in a solvent such as, but not limited to, hydrazine-dioxane, followed by hydroxylamine with acetic acid. In the presence of a reaction, a compound of formula (1902) is obtained. Alternatively, an acid compound of formula (1902) is treated with chlorinated herbicide in the presence of a catalytic amount of N,N-dimethylformamide to produce a corresponding A gasification oxime which, when reacted with a ruthenium compound such as, but not limited to, N-hydroxyethyl hydrazine in a solvent such as, but not limited to, pyridine, provides the oxadiazole product of formula (Iy). Preparation of a compound of formula (Iz) is a compound of the invention as set forth above in the Summary of the Invention, which can be prepared by the method set forth below in Reaction Scheme 2, wherein q and R16 and D are as defined above, q is an alkyl chain, an aralkyl group, an aryl group or a heteroaryl group: -185- 143924-sp-2009l 127-1 201020257 Reaction Scheme 20

The compound of the formula (2001) can be produced by a method known to those skilled in the art, or by the method disclosed in the present invention or by the method disclosed in the PCT Published Patent Application No. Hei. General β-reaction Scheme 20 is a schematic synthesis of a compound of the formula (Ιζ). The compound of the formula (2001) is treated with a strong base such as, but not limited to, sodium hydride to obtain a cyano compound of the formula (2002). (2〇〇2) and hydrazine, a reaction in a solvent such as, but not limited to, ethanol provides a compound of the formula (Ιζ)峨β. Preparation of the compound of the formula (Iza) The compound of the formula (Iza) is a compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method proposed in the reaction scheme 21, wherein q' R16' R20 and β are as defined above, which are referred to as an extended alkyl group or an aromatic or aryl or heteroaryl group. And r2〇 is an alkyl group, an aryl group or a heteroaryl group:

The compound of the formula (2101) can be produced according to the method known to those skilled in the art, or by the method disclosed in the present invention, or by the method disclosed in the PCT Published Patent Application No. 6/6/110,917. In general, Scheme 21 illustrates a schematic synthesis of a compound of formula (Iza). 143924-SP-20091127-1 -186- 201020257 An ester compound of the formula (2101), which is treated with hydrazine in a solvent such as, but not limited to, ethanol to obtain a hydrazine compound of the formula (2102) in an appropriately substituted anhydride or chlorine In the presence of a base such as, but not limited to, pyridine (also as a solvent), the product of formula (Iza) oxadiazole is provided. Preparation of the compound of the formula (Izb) The compound of the formula (Izb) is a compound of the invention as set forth above in the Summary of the Invention. Its $ is made by the method set forth below in Reaction Scheme 22, where R15 and W are both as defined above:

Reaction pattern 22

The compound of the formula (2201) can be prepared according to methods known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in the PCT Publication No. WO 2,6/110,917. .

In general, 'reaction pattern 22' is a schematic synthesis of a compound of formula (izb). The furan compound of formula (2201) is treated with hydrogen in the presence of a palladium catalyst such as, but not limited to, palladium on carbon in a solvent such as, but not limited to, ethyl acetate or decyl alcohol to provide the product of formula (Izb) tetrahydrofuran. Preparation of the compound of the formula (Izc) The compound of the formula (Izc) is a compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth below in Reaction Scheme 23, wherein both Ri6 and ® are as defined above, and (5) is a nitrogen-containing heteroaryl group: 143924-sp-20091127-1 •187· 201020257

Reaction pattern 23

The compound of formula (2301) can be used according to methods known to those skilled in the art, or by the methods disclosed herein, or by the method disclosed in PCT Patent Application No. WO 2006/110917. production. In general, 'reaction scheme 23' is a schematic synthesis of a compound of formula (IZC). Compounds of formula (2301), which are treated with an oxidizing agent such as, but not limited to, 3-p-perbenzoic acid in a solvent such as, but not limited to, dichloromethane, provide the oxide product of formula (he). Preparation of compounds of formula (Izd) and (Ize) The compounds of formula (Izd) and (Ize) are the compounds of the invention as set forth above in the Summary of the Invention. It can be made by the method set forth below in Reaction Scheme 24, wherein q, R15 and are as defined above: Reaction Scheme 24

143924-SP-20091127-1 201020257 The compounds of formula (2401) and (2402) can be used according to methods known to those skilled in the art, or by the methods disclosed herein, or by the PCT publication WO 2006/110917 Made by the method disclosed in the above. Compounds (2404) and (2405) are commercially available. In general, Reaction Scheme 24 illustrates the general synthesis of compounds of formula (Izd) and (Ize). a compound of formula (2401), which is treated with hydrazine in a solvent such as, but not limited to, dimethoxyethane, followed by reaction with isoamyl nitrite and hypophosphorous acid in a solvent such as, but not limited to, ethanol. A product of the formula (Izd) is provided. a compound of the formula (2401), which is an acetophenone (2404) or an acetone oxime (2405) in the presence of a base such as, but not limited to, a carbonic acid planing agent such as, but not limited to, hydrazine, hydrazine-dimethyl hydrazine. The treatment in guanamine provides the isoxazole product of formula (Ize). Alternatively, the compound of formula (2402) is treated with hydroxylamine to provide an intermediate of formula (2403) quinone imine which accepts an intramolecular Mitsunobu reaction to provide an isomeric olfactory product of formula (Ize). Preparation of a compound of the formula (Izf) The compound of the formula (Izf) is an inventive compound of the invention as set forth above in the Summary of the Invention. It can be prepared by the method set forth below in Reaction Scheme 25, wherein q, R15 and R16 are as defined above: Reaction Scheme 25

Compounds of formula (2501) may be as disclosed in the art, or by the method disclosed in the ' 143 924- s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s Made by the method. In general, Scheme 25 illustrates a schematic synthesis of a compound of formula (Izf). The compound of formula _), which is treated with an oxidizing agent such as, but not limited to, 3-chloroperbenzoic acid in a solvent such as, but not limited to, a two-gas methane, provides a product of the formula _ dioxide. The present invention is prepared by the method of the present invention as set forth in the preparation of the compound of the formula (Izg), and the compound of the formula (Izg) is as described above in the inventive composition. It can be as shown below in the reaction scheme 26 where the ruler 15, the ruler 16, the ruler 23 and the 0> are as defined above

In general, 'Reaction Scheme 26 is a schematic synthesis of a compound of formula (Izg). 143924-SP-20091127-1 • 190-201020257 The compound of formula (2601) is treated with hydrazine to obtain a reduced compound of formula (2602). (2602), obtained by treatment with a strong base such as, but not limited to, sodium hydride in a solvent such as, but not limited to, N,N-dimethylformamide followed by a reaction with the substituted 2_F_nitrobenzene A compound of formula (2604). (2604), for example, but not limited to, treatment of lithium bis(dimethylalkylalkyl)amine in a solvent such as, but not limited to, tetrahydrofuran, and reaction with methyl cyanoformate of formula (2605). (26〇5) The cyclized product of formula (2606) is obtained by hydrogen, in the presence of a catalyst, in the presence of a carbon, in a solvent such as, but not limited to, decyl alcohol. The compound of the formula (26〇6) is alkylated with the formula (26〇7) © a gas group or a bromine compound to give the product of the formula (Izg). Preparation of the compound of the formula (Izh) The compound of the formula (Izh) is a compound of the invention as set forth above in the Summary of the Invention. It can be produced by the method proposed by g in Reaction Scheme 27, wherein q, R1 5, R1 6 and hydrazine are as defined above.

Reaction pattern 27

The compound of the formula (27〇1) can be produced according to a method known to those skilled in the art, or by the method disclosed in the present invention, or by the method disclosed in the patent application p. General σ, reaction scheme 27 is a schematic synthesis of the compound of formula (izh).弋 () 5 substances, with E-type gas or two broken armor, in the presence of the test, = if not limited to saponin, in the solvent such as but not limited to tetrahydrofuran or 143924-sp-20091127-1 • 191 - 201020257 Treatment in Gu-dimethylformamide, providing a cyclized product. [Examples] The following preparations are directed to the preparation of intermediates for the preparation of the compounds of the present invention. The following examples are directed to the preparation of the compounds of the present invention, and the following biological examples are provided as guidelines to assist The invention is not intended to be limited by the scope of the invention. Preparation of 1 U-bis(hydroxymethyl)-3-(5-hydroxyindoleyl 4,3-benzoxazole group); synthesis of 1,3 dihydro-2H-indol-2-one .3.Hydroxy-3·(5-hydroxy.2-methyl.y·benzothiazole group) 4,}Dihydro-2H•indol-2-one synthesized in 2-methylbenzoindole Add isopropylmagnesium hydride (2M solution in tetrahydrofuran, 12.0) in chilled ((rc) solution in ozol-5-ol (4 gram, 24 〇 mmol) in anhydrous tetrahydrofuran (50 ml) ML, 24·〇 mmol. The resulting suspension was stirred at Ot for 5 hours and added in one portion (31 g, 21.2 mmol). The reaction mixture was taken at ambient temperature. Stir for 48 hours, and dilute with saturated aqueous ammonium sulfate (80 mL) and ethyl acetate (2 mL). Separate the liquid phase and extract the aqueous phase with ethyl acetate (3 x 5 mL). The combined organics were washed with brine (5 mL EtOAc) EtOAc (EtOAc m. Dry to give 3-hydroxy-3-(5- Benzyl-2-mercapto-l,3-benzopyrazolyl)-i,3-dihydro-2H-indol-2-one (4.11 g, 62%), m. (300 MHz, DMSO-d6) 5 10.34 (s, 1H), 10.02 (br s, 1H), 8.85 (br s, 1H), 7.78 (d, J = 8.6 Hz, 1H), -192- 143924-sp -20091127-l (S) 201020257 7.18-7.10 (m,1H), 7.01-6.74 (m,4H), 2.77 (br s,3H) ; MS (ES+) m/z 313 1 (M+l). · 3-(5-Lightyl-2-methyl-1,3-benzoxazol-6-yl)_1,3. Dihydro-2Η·哚哚·2_嗣 Synthesis of 3-hydroxy-3- (5- mercapto-2-mercapto-1,3-benzoxazole-6-yl)+3-dihydro-2Η_indol-2-one (4.81 g ' 15.4 mmol) and 48% hydrogen A mixture of aqueous iodic acid (25 ml) was heated under reflux for 1 hour. The reaction mixture was cooled to ambient temperature and diluted with water (50 mL) and ethyl acetate (5 mL). 'Cause sediment deposition. The solid was collected by filtration, washed with water (2 mL) and dried in vacuo to give 3-(5-hydroxy-2-methyl-1,3-benzo-pyrene-- 6-yl)-1,3-dihydro-2Η-indol-2-one (4.52 g, 99%), light yellow Body: MS (ES+) m/z 297.2 (Μ + 1) ° 1,3-bis(methyl)-3-(5-hydroxy-2-methyl-1,3-benzopyrazole_6_ Synthesis of 4,3. Dihydroanthracene·2·嗣 in 3-(5- mercapto-2-methyl-1,3-benzo-tomb _6_yl)_ι,3·dihydro_ Tendon-2_ketone (3. 66 g, 12.4 mmol), p-formaldehyde (1.85 g, 61.8 mmol) cooled in tetrahydrofuran (30 ml) and water (30 ml) (0 〇c In the suspension, a solution of sodium hydroxide (2.96 g, 74.1 mmol) in water (3 mL) was added dropwise. The reaction mixture was stirred at 0 <0>C for 1.5 h and was acidified to EtOAc EtOAc (EtOAc) The liquid phase was separated and the aqueous phase was extracted with ethyl acetate (3 X 50 mL). The combined organic solution was washed with brine (50 mL) dried over anhydrous sodium sulfate. The crude product was purified by column chromatography using ethyl acetate (yield from 67 to 100%) to give <3>3 bis(hydroxymethyl)_3_(5_hydroxy_2_ 143924-sp- 20091-127-l -193- 201020257 Methyl-1,3-benzopyrazol-6-yl)-l,3-dihydro-2H-indol-2-one (1.80 g '41%), as a colorless solid :iHNMRpOOMHz'DMSO-de) 9.79 (brs, 1H), 7.75 (d, J = 8.6 Hz, 1H), 7.23-7.15 (m, 1H), 7.11-7.06 (m, 1H), 6.94-6.80 (m , 3H), 6.21-6.14 (m, 1H), 5.95 (br s, 1H), 5.26-5.18 (m, 1H), 5.06-4.98 (m, 1H), 4.64-4.56 (m, 1H), 3.84- 3.76 (m, 1H), 2.80 (s, 3H); MS (ES+) m/z 379.0 (M + 23). Preparation of 2 6-bromo-1 -{[5-(trifluoromethyl)pyran-2-yl]methyl}spiro[1-benzofuran_3,3,-峋哚]-2' ( 1Ή)--Synthesis of ketone. 3·(4-Bromo-2·hydroxyphenyl)-3-hydroxy-1-{[5·(trifluoromethyl)- ran-2-yl]methyl-nitrogen Synthesis of -2Η·»5丨**多-2-网 In a stirred solution of 3-bromophenol (4.4 g, 25.4 mmol) in tetrahydrofuran (100 ml) at 〇 ° C, slowly Isopropylmagnesium chloride (127 ml, 2M tetrahydrofuran solution, 25.4 mol) was added. The mixture was stirred at 〇 °c for 3 〇 minutes and then the solvent was removed in vacuo. Add dioxane (1 mL) followed by 'addition of 1-((5-(trifluoromethyl))-yl)indoline-2,3 at 0 °C a solution of diketone (5.0 g, 16.9 mol) in dichloromethane (1 mL). The mixture was stirred at ambient temperature for 16 hours and quenched by the addition of saturated aqueous ammonium sulfate. The organic layer was washed with water and dried over sodium sulfate and concentrated in vacuo. The obtained solid is recrystallized from ethyl acetate/hexanyl to give 3-(4-bromo-2-hydroxyphenyl)-3-carbyl-1-{[5-(trifluoromethyl)anthracene , _2_ yl)methyl H,3-dihydro-2H-throin-2-one (6.4 g, 81%), as a colourless solid: NMR (300 MHz, DMSO-d6) 5 7.49-5.83 (m, 9H), 5.13-4.71 (m, 2H); MS (ES+) m/z 449.9 (Μ - 17), 451.9 (Μ - 17). 143924-sp-20091127-l •194- 201020257 Β. 3-(4·Bromo-2-hydroxyphenyl)-1·{[5-(trifluoromethyl) ran-2-yl] decyl Synthesis of 1,3-di-argon·2Η-,5-p-but-2-one ketone 3-(4-bromo-2-hydroxyphenyl)-3-carbyl-1-{[5-(trifluoromethyl) Furan-2-yl]methyl}-1,3-dihydro-2Η-4哚-2-one (5.5 g, 11.8 mmol), triethyldecane (20.0 mL, excess) and trifluoro A mixture of acetic acid (20.0 mL, excess) was stirred at ambient temperature for 16 h. The mixture was concentrated under vacuum. The residue was treated with diethyl ether to form a suspension. Filtration to obtain 3-(4-bromo-2-hydroxyphenyl)-1-{[5-(trifluoromethyl)>indol-2-yl]methylhydrazine, 3-dihydro-2-indole-indole Indole-2-one (4.3 gram '82%) ' is a colorless solid: 1H NMR (300 MHz, CDC13) <5 8.91 (br s,1 Η), 7.36 (t, J = 7.9 Hz, 1H), 7.26 -7.13 (m, 2H), 7.05 (d, J = 7.9 Hz, 1H), 6.97 (d, J = 2.0 Hz, 1H), 6.92 (dd, J = 8.5, 2.0 Hz, 1H), 6.73-6.67 ( m, 2H), 6.35 (d, J = 3.5 Hz, 1H), 5.08 (s, 1H), 4.95 (s, 2H) ; MS (ES+) m/z 452.0 (M + 1), 450.0 (M+l C. 6-Bromo-based 1'·{[5·(Trifluoromethyl)pyran.2_yl]methyl}spiro[i_benzofuran·3,3,_ 吲哚W(l 'H)·ketone under argon at 3-(4-bromo-2-hydroxyphenyl) small {[5-(trifluoromethyl)pyran-2-yl]methyl}-1,3 - dihydro-2H-indol-2-one (4.3 g, 9.5 mmol), chloromethyl iodide (1.8 ml, 25.3 mmol) in a stirred solution in tetrahydrofuran (1 mL) 'Addition of carbonic acid (9.9 g, 30.5 mmol). The mixture was stirred at ambient temperature for 16 hours and then filtered through a pad of Celite. The filtrate was concentrated in vacuo. Treated to give 6-bromo-indenyl-{[5-(trifluoromethyl)pyranyl]fluorenyl}spirobenzofuran_3,3,-indole 2'(1Ή)-one (3.46 g '78%) ' is a colorless solid: iHNMR (300MHz, CDC13) <5 7.30 (td, J = 7.9, 1.5 Hz, 1H), 7.16-7.03 (m, 3H), 6.69 (d, J = 7.9 Hz, 1H), 143924-SP-20091127-1 -195- 201020257 6.93 (dd, J = 8.2, 1.8 Hz, 1H), 6.77-6.71 (m, 1H), 6.53 (d, J = 8.2 Hz, 1H), 6.42 -6.37 (m, 1H), 5.06 (d, J = 16.1 Hz, 1H), 4.97 (d, J = 9.4 Hz, 1H), 4.86 (d, J = 16.1 Hz, 1H), 4.71 (d, J = 9.4 Hz, 1H) ; 13 C NMR (75 MHz, CDC13) δ 176.5, 161.5, 151.8, 141.4, 131.6, 129.3, 128.0, 124.5 (d), 124.0, 114.2, 112.6 (d), 109.2 (d), 80.1 , 57.5, 36.9; MS (ES+) m/z 463.9 (M + 1), 465.9 (M + 1) 〇 Preparation 3 1-(Diphenylmethyl)-3-(2-hydroxy-4-methoxy- Synthesis of 5-nonylphenyl)-1,3-dihydro-2H-indol-2-one _ A. 1-(Diphenylmethyl)·3-hydroxy-3-(2-hydroxy·4· Synthesis of decyloxy-5-methylphenyl)-1,3-dihydro-2H-"?丨哚-2-_ at 0C in 3-decyloxy-4-nonylphenol (jorgensen, E c et al., j. C. (1971), 14: 1199 · 202) (7.5 g, 54 3 mmol) in a stirred solution of dioxane (10 ml), add isopropyl magnesium hydride (29 mL, 2 Torr, in tetrahydrofuran, 58 mmol) ). The resulting mixture was placed in a crucible. The mixture was stirred for 30 minutes, followed by the addition of 丨_diphenylmethyldihydrop?丨哚-2,3dione (4 g, 36.3 mmol). The reaction mixture was stirred at ambient temperature for a few minutes, 13 and concentrated in vacuo to dryness. The residue was dissolved in ethyl acetate (10 mL) and washed with EtOAc (2×2 mL). The ethyl acetate layer was dehydrated and dried with sulfuric acid, filtered, and concentrated in vacuo to give benzoic acid > 3-carbyl-3·(tetra)yl-4-ylmethoxymethyl & Take dihydro., indole-2-one (19.10 g)' as a crude brown oil: paper can be purchased as a can. Β·1 Benzylmethyl)-3_(2_transalkyl-4_methoxyjmethyl & phenyl-like diazepane·2·one ketone synthesis 143924-sp-20091127-l * 196- 201020257 At 〇 ° C, in 1-(diphenylmethyl)_3_hydroxy_3_(2-hydroxylmethoxy_5曱yl)-1,3-one wind_2Η-Ί丨〃--2 - a stirred mixture of a ketone (15.4 g, 34.1 mmol) and =ethyl oxalate (15 ml), trifluoroacetic acid (seven) ml was added and the solution was stirred at ambient temperature for 16 hours and concentrated in vacuo. The residue was recrystallized from diethyl ether (25 ml) in a water bath on a Branson Ultrasonic Workbench to give 1-(diphenylmethyl)_3_(2-hydroxyindoleyl-5-phenylbenzene H'3-dihydro-2H4indol-2-one (11.0 g, cc%) as a colorless solid: 丨H nmr (300 MHz, CDC13) (5 7.42-7.16 (m, 12H), 7.11-7.01 (m, 2H)>6>94 (s? 1H)> ® 6.61 (s, 1H), 6.57-6.49 (m, 1H), 6.45 (s, 1H), 5.08 (s, 1H), 3.63 ( s, 3H), 2.03 (s, 3H); MS (ES+) m/z 436.3 (M + 1). Preparation 4 4-chloro-l-(l-methyl)-3-(6-carbyl) 2,3-dihydro-1-benzo-campyl)_ι 3_ dihydro-2H-W哚-2-one Synthesis of A. 4 · gas-based · 1 · (diphenylmethyl) 1 H 蚓哚 · 2, 3 · dione synthesis at 0 C 'in 4- gas based 4 Bu Duo (9.10 g, 50.0 mmol) Sodium hydride (2.20 g, 55.0 mmol) was added to a stirred solution of ν, Ν-二chun methyl methamine (100 ml). The reaction mixture was stirred at 0 ° C for 1 hour, then Bromodiphenylmethane (14.80 g, 56.8 mmol) was added. The mixture was stirred at ambient temperature for 20 hours. The mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was crystallised from diethyl ether and hexane to give 4-chloro-l-(diphenyl)

Base)-1Η-峋哚-2,3-dione (14.20 g, 81%): 1H NMR (300 MHz, CDC13) (5 7.37-7.17 (πχ, 11H), 6.98-6.95 (m, 2H), 6.42 (d, J = 9.0 Hz, 1H); MS (ES+) m/z 369.9 (M + 23), 371.9 (M + 1). 143924-sp-20091127-1 •197· 201020257 Β· 4-gas base ·1·(Diphenylmethyl)-3-lightyl-3-(6-radio- 2,3-diaza-1-benzo-bate 5-yl)-1,3-diaza-2Η- The synthesis of Ή丨嗓-2-嗣 was carried out according to the procedure described in Preparation 3, and the irrelevant change was carried out, and the 3-methoxy-4-indenyl group was replaced with 2,3-dihydrobenzofuran-6-ol. Phenol, and the use of 4-alkyl-1-(diphenylfluorenyl-2,3-dione to replace 1-diphenylmethyldihydro, 丨 丨 -2,3-·一嗣' -oxyl-1-(diphenylmethyl)-3-carbyl-3-(6-carbyl-2,3-diar-arsen-1-benzoin-5-yl)-1,3-di Hydrogen-2Η-Θ卜朵-2- Stuff | (87%), beige solid: 4 NMR (300 MHz, CDC13) (5 8.66 (br s, 1H), 7.36-7.16 (m, 10H), 7.05 -7.01 (m, 2H), 6.89 (s, 1H), 6.58 (s, 1H), 6.45-6.38 (m, 2H), 4.57-4.49 Θ (m, 2H), 4.03 (br s, 1H), 3.13 -2.91 (m, 2H) ; MS (ES+) m/z 505.9 (M + 1), 507.9 (M + 1) C. 4-Alkyl-1-(diphenylmethyl)·3·(6.Hydroxy-2,3•dihydrobenzobenzofuran_s•ylnitrogen_2H·,?丨嗓_2 _嗣 is synthesized in 4-gas-based small (diphenylmethyl)_3_hydroxy_3 (6-hydroxy-2,3 dihydrobenzobenzopyran-5-yl)-1,3-dihydro-2Η-啕哚_2 ketone (9.25 g, 19" millimolar) in dichloroa

In a solution of turbid 5 ml), add triethyl sulphate (10 ml). The mixture was allowed to cool to 〇t, then tri-acetic acid (9 mL) was slowly added over 5 min. The resulting mixture was stirred at ambient temperature for 5 hours and concentrated in vacuo to dryness. The residue was taken up in diethyl ether (25 mL).

Developed in water cooling on k on the Branson Ultrasonic Workbench, resulting in 4_gas-based small (diphenylmethyl)-3-(6-pyridyl-2,3-dihydro and +1 wind and scented ·5-yl)-1,3_dihydro-2H_嘀哚_2_ ketone (8.90 g, quantitative), mino-polygon color solid: MS (ES+) m/z 468.0 (M + 1), 470.0 (Μ + 1). Preparation 5 143924-sp-20091127-1

-198- 201020257 3-(4-Api-2-ylphenyl(diphenylfluorenyl)_u_dihydro-2H(4)哚_2-one synthesis Α·3·(4-xiyl_2-hydroxybenzene Synthesis of 3-bromo-enzymidine (u.9 g, 69 2 mmol) in dichloro In a stirred solution of methane (16 mL), isopropylmagnesium hydride (2.0 Torr, 38.0 mL of '76 J mM in tetrahydrofuran) was added under TC. The solution was stirred under 〇〇c. After 3 minutes, 1-diphenylmethyldihydroindole-2,3-dione (1 Torr, gram, 34.6 mmol) was added. The reaction was stirred at ambient temperature for 16 hours, then vacuum The residue was dissolved in ethyl acetate (400.0 ml) and washed with saturated aqueous ammonium sulfate (3 X loo. And concentrated to dryness in vacuo. Purification by flash chromatography, using 30% ethyl acetate in the compound to give 3-(4-bromo-2-phenyl)-indole-methyl) 3-Phenyl-1,3-dihydro-2H-indol-2-one (11.7 g, 70%) as a beige solid: i H NMR (300 MHz, CDC13) <5 9.09 (br s,1H), 7.47-7.16 (m, 11H), 7.12-7.00 (m, 3H), 6.92-6.84 (m, 2H), 6.72-6.66 ( m, 1H), 6.51-6.45 (m, 1H), 4.57 (br s, 1H) ; MS (ES+) m/z 484.2 (M + 1), 486.2 (M + 1). Β· 3_(4·漠Synthesis of 2-(4-carbyl-2-hydroxyphenyl)-1 benzylidene by benzyl-2-hydroxyphenyl)succinyl(diphenylmethyl)+3 dihydro-2H•indole-2-one _3_carboxyindole-dihydro-2H, indole-2-one (13.1 g ' 27.1 mmol) in triethyl decane (25.0 ml) in ice-cold stirred solution, added trifluoroacetic acid (25.0 ml) ). The solution was stirred at ambient temperature for 64 hours' then concentrated to dryness in vacuo. Recrystallization from diethyl ether (25.0 ml) in a water bath on a Brans〇n ultrasonic bench gave 3-(4-bromo-2-hydroxyphenyl-H-(diphenylmethyl)-di-argon-2H_吲哚 ketone (1〇! 143924-sp-20091127-1 •199- 201020257 gram '79%), as a colorless solid: iHNMR (300MHz, CDCl3) 5 9.17 (s, 1H), 7.40-7.03 (m, 13H), 6.99-6.92 (m, 2H), 6.79-6.74 (m, 2H), 6.58-6.50 (m, 1H), 5.10 (s, 1H) ; MS (ES-) m/z 468.2 (M -1 ), 470.2 (M -1). Preparation 6 1-(Diphenylfluorenyl)_3_(2-hydroxy-4,5-diindenylphenyl) 4,3-dihydro-2H_indole-2-one Synthesis of A. 1-(Diphenylmethyl)-3-hydroxy-3-(2-hydroxy-4,5-dimercaptophenyl)-1,3-dihydro-2H-W哚·2·one Add isopropylmagnesium chloride (1〇2 ml, 2.0M IV) in a stirred solution of 3,4-xylenol (2.50 g, 20.5 mmol) in tetrahydrofuran (100 ml) at 〇 °C Hydrogen p lost solution, 20.40 millimoles. The mixture was stirred at 〇 °c for 1 hour' then the solvent was removed in vacuo. Dioxane (2 mL) was added followed by 1-(diphenyl)曱基)_1H-吲哚_2,3_dione gram, 15 95 Mo ear). The mixture was stirred at ambient temperature for 54 hours and the reaction was quenched with saturated aqueous ammonium sulfate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and evaporated. The filtrate is concentrated in vacuo, and the residue is purified by column chromatography to give 1-(dihydromethane) hydroxy-hydroxyl-(2-hydroxy- 4,5-dimethylphenyl yl)-1. 3-Dihydro-2H-indol-2-one (5·1 g, 73%) : β NMR (300 MHz, CDC13) δ 7.49-7.45 (m, 1H), Ί35-121 (m, 10H) , 7.08-7.04 (m, 2H), 6.93 (s, 1H), 6.81-6.75 (m, 1H), 6.52 (s, 1H), 6.49-6.46 (m, 1H), 2.15 (s, 3H), 2.02 (s, 3H) ; MS (ES+) m/z 418.1 (M -17). Synthesis of Β· 1-(diphenylmethyl)-3-(2-hydroxy-4,S-dimethylphenyl) 4,3 dihydro 2H, 哚 2 ketone as described in Preparation 4C Procedure, and the implementation of irrelevant changes, 143924-sp-20091127-1

CS *200. 201020257 Using 1-(diphenylindenyl)-3-hydroxy-3-(2-hydroxy-4,5-dimethylphenyl)-l,3-dihydro-2H, indole-2- Ketone replacement of 4-oxyl-1-(diphenylfluorenyl)-3-hydroxy-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1,3-di Hydrogen-2H-indol-2-one, 1-(diphenylindenyl)-3-(2-hydroxy-4,5-dimethylphenyl)-1,3-dihydro-2H-indole 2-ketone (93%): 1Η NMR (300 MHz, CDC13) δ Ί3Λ-121 (m, 11Η), 7.06-7.02 (m, 3H), 6.76 (s, 1H), 6.72 (s, 1H), 6.55-6.50 (m, 1H), 5.05 (s, 1H), 2.17 (s, 3H), 2.12 (s, 3H); MS (ES+) m/z 420.2 (M + 1). Preparation of 7 ® quinone diphenylmethyl)-5-f-yl-3-(6-carbyl-2,3-dihydro-1-benzopyran-5-yl)-1,3-dipho-2H Synthesis of -p5j嗓-2-嗣 A. Synthesis of 1-(diphenylfluorenyl)-5·fluoroyl-1Η-Θ丨嗓-2,3-di-class at 5-°C Strontium (16 g, 36.3 mmol) in a stirred solution of N,N-dimercaptocaramine (50 ml) was added sodium hydride (16 g, 4 〇········ The reaction mixture was stirred at 0 ° C for 1 hour then bromodiphenylmethane (10.0 g, 38.0 m. The mixture was stirred at 6 ° C φ for 7 hours, diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to dryness in vacuo and the residue was recrystallised from ethyl acetate and hexanes to give i (diphenyl hydrazyl) _5 fluoro-1H-decao-2,3-dione (6.3 g) , 52%) : iH NMR (3〇〇MHz, CDCl3) δ 7.39-7.27 (m, 11Η), 7.04-6.97 (m, 2H), 6.46-6.42 (m, 1H) ; MS (ES+) m/z 354.2 (M +23). B. 1-(monophenylmethyl).s_fluoroyl_3_hydroxy_3_(6•hydroxy-2,3-dihydropicordol-5-yl)-1,3·dihydro-2H ·, the synthesis of ketone 2 ketone according to the procedure as described in Preparation 6Α, and the implementation of the insignificant change, 143924-sp-20091127-1 -201- 201020257 using 2,3-dihydrobenzofuran-6- Alcohol replacement of 3,4-xylenol, and replacement of 1-(diphenylmethyl)-111-' with 1-(diphenylindenyl)-5-fluoro-111-indole-2,3-dione 15丨哚-2,3-dione's 1-(dihydromethane)-5-fluoro-3-carbyl-3-(6-carbyl-2,3-dioxin-1-benzo吱-5-yl)-1,3-dihydro-2H-W fluoren-2-one (99%): 4 NMR (300 MHz, CDC13) δ 8.94 (s, 1H), 7.36-7.19 (m, (H, 1H) s, 1H), 3.06-3.00 (m, 2H); MS (ES+) m/z 466.4 (M -1) 0 C· 1-(Diphenylmethyl)-5-fluoro-3-(6-hydroxyl Synthesis of -2,3-dihydrobenzobenzopyran-5-yl)-1,3->-azepine-2·嗣 according to the procedure as described in Preparation 4C, and performing irrelevant changes, using 1-(monomethyl)-5-fluoro-3-carbyl-3-(6-carbyl- 2,3-Dihydro-1-benzocypan-5-yl)-1,3-dihydro-2H-indol-2-one Substituted 4-Alkyl-1-(diphenylfluorenyl)- 3-carbyl-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-[[3-dihydro-2H-indol-2-one, 1- (Diphenylfluorenyl)-5-fluoro-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1,3-dihydro-2H-indole-2 -ketone (94%): mp 9-181 Χ: (methanol); 1 H NMR (300 MHz, CDCI3) δ 7.36-7.19 (m, 11H), 7.02-6.97 (m, 2H), 6.77-6.69 (m, (H, 2H) + 1) Preparation of 8 1-(diphenylfluorenyl)-6-fluoro-3-(6-carbyl-2,3-dihydro-1-benzofuran-5-yl)-l,3- Synthesis of dihydro-2H-indole-2-one A. Synthesis of 1 benzylidene) 6-fluoro-1H-P5 bromo-2,3-dione according to the procedure as described in Preparation 4A, And the implementation of insignificant changes, the use of 6-fluoro hydrazine (Sadler, P. W., 乂〇 c/iem. (1956), 21 (2): 169-70) 143924-SO-20091127-1 201020257 Replacement of 4-chloro hydrazine to obtain ι_(diphenylmethyl)_6-fluoro-1H-indole-2,3-dione (76%): fused 167-1691 (diethyl ether); 1H NMR (300 MHz, DMSO-d6) 3 7.41-7.27 (m, 11H), 6.77 (s, 1H), 6.30-6.26 (m, 1H), 5.82-5.80 (m, 1H MS (ES+) m/z 354.1 (M + 23). Β· 1-(Diphenylmethyl).6-fluoro-3-hydroxy-3·(6-hydroxy-2,3-dihydro-1-benzo-flavor-5-yl)-1,3· Synthesis of dihydro·2Η·»^嗓-2-嗣 Follow the procedure described in Preparation 6Α, and perform irrelevant changes, using 2,3-H benzo? Fus -6-alcohol replacement 3,4-didecyl, and 1-(diphenylindenyl)-6-fluoro-l-indole-2,3-dione in place of 1-(diphenyl) Methyl)-1Η-啕哚-2,3-dione to give 1-(dimethylene)-6-fluoro-3-hydroxy-3-(6-hydroxy-2,3-dihydro-1 -benzofuran-5-yl)-1,3-dihydro-2-indole-thin-2-one (84%): mp 147-149eC; 1H NMR (300 MHz, CDC13) δ 8.80 (s, 1 Η) , 7.44-7.20 (m, 11H), 6.90 (s, 1H), 6.79-6.72 (m, 1H), 6.59 (s, 1H), 6.45 (s, 1H), 6.20-6.17 (m, 1H) ; MS (ES+) m/z 450.1 (M - 17) ° C. 1-(Diphenylmethyl)-6-fluoro-3-(6-hydroxy-2,3·dihydro-1-benzofuran.5 _base)-

Synthesis of 1,3-dihydro-2HMindole-2-one A. According to the procedure described in Preparation 4C, and irrelevant changes were made using 1-(diphenylfluorenyl)-6-fluoro-3- Hydroxy-3-(6-hydroxy-2,3-dihydro-1-indole-5-yl)-1,3-dihydro-2H-indol-2-one substituted 4-alkyl-1 -(diphenylfluorenyl)-3-hydroxy-3-(6-hydroxy-2,3-dihydro-1-phenyl.furan-5-yl)-1,3-dihydro-2H-indole- 2-ketone'-l-(diphenylhydrazinyl)-6-yl-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1,3-dihydrogen -2H-chonon-2-one (99%): m.p. 121-123°C (methanol); 1H NMR (300 MHz, CDCI3) δ 7.36-7.16 (m, 11H), 6.95 (s, 1H), 6.77 -6.71 (m, 1H), 6.67 (s, 1H), 6.46 (s, 1H), 6.25-6.21 (m, 1H), 5.00 (s, 1H), 4.53 (t, J = 9.0 Hz, 143924-sp -20091127-1 -203- 201020257 2H), 3.08-3.01 (m, 2H); MS (ES+) m/z 451.9 (Μ + 1). Preparation 9 3-(6-Hydroxy-3-methyl-1,2-benzisoxazole·5-yl) small (4-decyloxybenzyl)_i,3_di A.3·hydroxy-3 -(6-hydroxy-3-methyl-1,2·benzisoxazole-5-yl)-1-(4-methoxyindenyl)-1,3-dihydro·2Η4哚-2· The synthesis of the ketone is carried out according to the procedure described in Preparation 6, and the insignificant changes are made using 3-methylbenzo[d]isoxazol-6-ol (Imnpoor, Ν. et al., and - (2006) , 47 : 8247) Displacement of 3,4-xylenol' and replacement of 1-(diphenylmethyl)_ιη·吲嗓 with ι_(4-methoxybenzyl)_1H_ 吲嗓-2,3-dione 2,3-dione to give 3-carbyl-3-(6-hydroxy-3-indolyl-1,2-benzisoxazole-5-yl)-1-(4-methoxyindenyl) )_ι,3_ dihydro-2H-W嗓_2-ketone (%%): melting point ["々ore (ethyl acetate); 1 η NMR (300 MHz, DMSO-d6) 5 7.52 (d, J = 9.0 Hz, 1H), 7.37 (d, J = 9.0 Hz, 2H), 7.18-7.13 (m, 1H), 7.05-7.03 (m, 1H), 6.89-6.75 (m, 5H), 4.83 (AB, 2H ), 3.71 (s, 3H), 2.77 (s, 3H); MS (ES+) m/z 417.0 (M + 1). B. 3-(6-Hydroxy-3-methyl-1,2-benzisoxazole-5-yl) small (4-methoxybenzyldihydro-2Η-«»5丨"-2 - synthesis of 嗣

Lower base)-1'3-dihydro-2H-throin-2-one (3.70 g; 8.9 mmol) and triethyldecane (8.4 ml, 52.6 mmol) in the second stage of the test, Hey.

Saliv-5-yl)-1-(4-methoxyindenyl)_U-di(3)(6-hydroxy-3-methyl-1,2-benzisoindole>-1'3- Dihydro-2Η-吲哚_2·one (3.34 g, 143924-SP-20091127-1 -204- 201020257 93%): melting point 195-197 ° C (diethyl ether / hexane); 1H NMR (300 MHz, CDC13 ) (5 7.37 (d, J = 9.0 Hz, 2H), 7.19-7.14 (m, 1H), 7.03-6.81 (m, 6H), 6.42 (d, J = 9.0 Hz, 1H), 5.46 (s, 1H) ), 5.04 (Aq, 2H), 3.74 (s, 3H), 2.43 (s, 3H); MS (ES+) m/z 401.0 (M + 1). Preparation of l〇1-diphenylmethyl-3-( Synthesis of 5-fluoro-2-hydroxy-4-methoxyphenyl)indan-2-one A· 1-(diphenylfluorenyl)-3-(5-fluoro.2-hydroxy-4 Synthesis of -methoxyphenyl)-3-hydroxy-1,3-dihydro-2-indol-2-one® According to the procedure described in Preparation 6Α, and applying irrelevant changes, 4-fluoro Substituting 3,4-xylenol for methoxy phenol to obtain 1-(diphenylmethyl)-3-(5-fluoro=2-hydroxy-4-methoxyphenyl)-3-hydroxy-1 ,3-Di-argon-2Η-indol-2-one (95%): 1H NMR (300 MHz, CDC13) 6 9.50-9.00 (br,1Η), 7.48-7.41 (m, 1H), 7.36-7.25 ( m, 8H), 7.22-7.16 (m, 2H), 7.14-7.07 (m, 2H), 6.88 (s, 1H), 6.64 (d, J = 7.5 Hz, 1H), 6.56-6.46 (m, 2H), 4.43-4.00 (br, 1H), 3.81 (s, 3H), MS (ES+) m/z 456.1 (M + 1) Β·H Diphenylmethyl)-3-(5-1-yl-2-hydroxy-4.methoxyphenyl)-1,3-dihydro-2H-indole-2- The synthesis of the ketone was carried out according to the procedure as described in Preparation 3B, and the insignificant change was made using 1-(diphenylmethyl)-3-(5-fluoro-2-hydroxy-4-indoleoxyphenyl)- Displacement of 3-(diphenylhydrazinyl)_3_carbyl_3_(2-hydroxyindoleoxy-5-methylphenyl) by 3-yl-1,3-dihydro-2H-indol-2-one -i,3-dihydro-2H-W哚-2-one, 1-(diphenylindenyl)-3-(5-yl-2-hydroxy-4-methoxyphenyl) 4} dihydrogen -2H-indol-2-one (73%) : 1H NMR (300 MHz, CDC13) <5 9.33-8.84 (br, 1H), 7.41-7.25 (m, 9H), 7.22-7.04 (m, 4H ), 6.92 (s, 1H), 6.71 (d, J = 7.7 Hz, 1H), 6.64 (d, J = 12.2 Hz, 1H), 143924-sp-20091127-1 -205- 201020257 6.56-6.49 5.09 3.84 ( s,3H); MS (ES+) m/z 440.1 (M + 1) 0 Preparation of 11 H diphenylmethyl)-3-(5-fluoro-2-phenyl) 4,3_dihydro_2H_ +Synthesis of a pin Α·1·(diphenylmethyl)-3-(5-fluoro 2-hydroxyphenyl)-3-hydroxy-7-3-dihydro·2H Synthesis of 吲哚•2-明 According to the procedure as described in Preparation 6A, and irrelevant changes were made, 3,4-xylenol was replaced with 4-fluorophenol to obtain 丨_(diphenylmethyl) 3 ( 5-fluoro 2-bromo-2-phenyl-1,3-dihydro-2H-indol-2-one (76%) : 1H NMR (300 MHz, CDC13) ^ 7.47-7.39 (m, 1H ), 7.37-7.19 (m, 10H), 7.14-7.06 (m, 2H), 6.94- 6.87 (m, 3H), 6.62-6.55 (m, 1H), 6.53-6.45 (m, 1H) ; MS (ES+ ) m/z 448.0 (M + 23). Synthesis of Β· 1-(diphenylmethyl)-3-(5-fluoro-2-hydroxyphenyl wj·dihydro·2Η-吲哚_2-one according to the procedure as described in Preparation 3B, and An insignificant change was made using 1-(diphenylmethyl)-3-(5-fluoro-2-hydroxyphenyl)-3-hydroxy-1,3-dihydro-2H-choline-2-net Displacement of 1-(diphenylmethyl)_3_transcarbyl_3_(2-hydroxy-4-methyl-5methylphenyl)-1,3-dihydro-2H-indol-2-one (Diphenylmethyl)_3_(5-fluoro-2-hydroxyphenyl)-1,3-dihydro-2H-indol-2-one (78%): 1H NMR (300 MHz, CDC13) < 5 8.80 (s, 1H), 7.39-7.26 (m, 9H), 7.22-7.16 (m, 2H), 7.15-7.05 (m, 2H), 7.05-6.97 (m, 1H), 6.96-6.85 (m, 2H), 6.68-6.61 (m, 1H), 6.58-6.50 (m, 1H), 5.16 (s, 1H); MS (ES+) m/z 410.0 (M + 1). Preparation 12 1-(diphenylhydrazine) Synthesis of 3-(2-hydroxy-4-methoxyphenyl)-1,3-dihydro-2H-indol-2-one 143924-SP-20091127-1 •206· 201020257 Α· 1- Synthesis of (diphenylfluorenyl).3 hydroxy _3·(2_hydroxy-4 methoxyphenyl)qj·dihydro·2H 丨哚-2-嗣 according to the procedure as described in Preparation 6A, and the implementation is irrelevant A critical change, replacing 3,4-dimethyl with 3-methoxyphenol , 1-(Diphenylfluorenyl)_3_carbyl-3-(2-pyridyl-4-hydrazinophenyl)-, 3-dihydro-2H-indol-2-one (99%): MS (ES+) m/z 420.2 (Μ -17), 460.2 (Μ + 23). Β· 1-(diphenylmethyl)-3_(2-yl-4-methoxyphenyl)·1,3 Synthesis of dihydro-2-indole-indolo-2-one at ambient temperature in the presence of 1-(diphenylhydrazinyl)-3-hydroxy-3-(2-hydroxy-4-methoxyphenyldihydro- 2Η-Indol-2-one (27.9 g, 63.8 mmol) in a solution of di-methane (200 mL). The reaction mixture was refluxed for 15 hr. The mixture was concentrated to dryness in vacuo. EtOAc EtOAc m. 2_Hydroxy methoxyphenyl) 4,3-dihydro-2 fluorene-< fluoren-2-one (7.40 g, 27%) as colorless solid: iH NMR (3 〇〇MHz, CDC13) 5 7.40-7.18 (m, 11H), 7.13-7.06 (m, 2H), 6.97 (s, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.67-6.64 (m, 1H), 6.57-6.52 (m, 1H) ), 6.41 (dd, J = 8.4, 2.4 Hz, 1H), 5.11 (s, 1H), 3.77 (s, 3H). Preparation of 13 H Diphenylmethyl)-3-(7-hydroxy-2,3-dihydro-i,4-benzodioxanthene, H,3-dihydro-2H-indol-2-one Synthesis of A. 1_(diphenylmethyl)-3-hydroxy-3-(7-hydroxy-2,3-dihydro·ι,4·benzodioxol-6-yl>1,3 Synthesis of dihydro-2Η-Η丨嗓.2 ketone according to the procedure as described in Preparation 6Α, and the implementation of irrelevant changes, 143924-sp-20091127-1 -207- 201020257 using 2,3-one wind Replacement of 3,4-dimethylhydrazine with benzo[b][l,4]dioxanthene--6-ol to obtain 1-(diphenylindenyl)-3-yl-3-yl-7-yl -2,3-dihydro-l,4-benzodioxanthracene-6-yl)-1,3-dihydro-11-2-one (88%) 'Light yellow powder: mp 210- 212 C (water)·' 1H NMR (300 MHz, DMSO-dg) 6 9.08 (br s,1H), 7.42-7,24 (m, 11H), 6.97-6.79 (m, 4H), 6.54 (br s , 1H), 6.29 (d, J = 7.8 Hz, 1H), 6.17 (s, 1H), 4.25-4.13 (m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.8, 143.0, 142.7, 138.3 , 137.8, 128.5, 128.4, 128.3, 128.0, 127.6, 127.4, 123.7, 121.6, 120.8, 115.6, 110.8, 103.3, 74.1, 64.4, 63.8, 57.2 I MS (ES+) m/z 488.2 (M + 23) 〇B . 1- (two Methyl)-3-(7-transyl-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3-diargon-2H-,?丨嗓· Synthesis of 2-indole according to the procedure described in Preparation 4C, and irrelevant changes were made using 1-(diphenylfluorenyl)-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1 , 4-benzodioxanthene-6-yl)-1,3-dihydro-211-4丨ρ-2-one substituted 4-alkyl-1-(diphenylfluorenyl)-3- Hydroxy-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1,3-dihydro-2Η-indol-2-one, 1-(diphenyl) Methyl)-3-(7-transyl-2,3-dihydro-1,4-benzodioxan-6-yl)-1,3-dihydro-2Η-吲嗓-2- Ketone (quantitative), light pink solid: mp 157-160 ° C (diethyl ether / hexane); 1H NMR (300 MHz, DMSO-d6) 5 9.19 (br s, 1H), 7.42-7.27 (m, 10H ), 6.98-6.91 (m, 3H), 6.88-6.82 (m, 1H), 6.69-6.63 (m, 1H), 6.37 (d, J = 7.8 Hz, 1H), 6.30 (s, 1H), 4.81 ( s, 1H), 4.21-4.11 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 176.2, 149.2, 142.8, 142.6, 138.2, 137.8, 135.8, 130.1, 128.6, 128.4, 128.3, 128.2, 127.7 , 1275, 126.8, 123.6, 121.7, 118.9, 117.0, 110.6, 103.8, 64.3, 6 3.8, 57.4, 47.4; MS (ES+) m/z 450.3 (M + 1). 143924-sp-20091127-l -208- 201020257 Preparation 14 1-(Diphenylmethyl)_3_(7_carbyl_3,4_di-argon-2H•cut _6-like dichloro-indole-2- _ Synthesis of Α·1 仁 “Methyl)-3-carbyl _3_(7· carbyl _3,4. diammonium 2h • bite-based genomic dihydro-2H is 丨哚-2-one synthesis

于 于克7 Alcohol (Cube, RV, etc., listen to ^^^ hunger (2〇〇5), 15(9): 2389-93) Shike, 3.66 millimolar) in tetrahydrofuran ( ιι Cooling (0C) in ML) ♦ In-liquid isopropyl chloride chlorination (2.4 ml, in THF, 4.8 mmol) was added under nitrogen. The resulting solution was stirred for 30 minutes. A suspension of 1-(diphenylmethyl)indoline-2,3•dione (1.16 g, 3 7 mmol) in di-methane (4 mL) was added. The reaction was stirred at 〇t: for 10 min then warmed to ambient temperature and stirred for 155 h. The reaction was diluted with a saturated aqueous solution of ammonium chloride (10 ml), and the organic solvent was removed under reduced pressure. The residual mixture was diluted with water (50 mL) andEtOAcEtOAc. The combined organic solution was washed with brine (5 mL EtOAc) The residue was purified by flash column chromatography using hexane/ethyl acetate (7:3) to give (diphenylmethyl)-3-ylidene-3-(7-carbyl-3,4 -Dihydro-2H-p-gram-6-yl)-1,3-dihydro-2Η-Θ| Ind-2-one (1.37 g, 81%) 'Light yellow solid: Refining point 204-206° C (diethyl ether / hexane); 1H NMR (300 MHz, CDC13) 5 8.90 (s, 1H), 7.49 (dd, J = 5.6, 3.2

Hz, 1H), 7.38-7.23 (m, 10H), 7.12-7.06 (m, 2H), 6.95 (s, 1H), 6.52-6.47 (m, 3H), 4.23 (s, 1H), 4.121 (dd, J = 5.7, 4.5 Hz, 2H), 2.53 (t, J = 6.3 Hz, 2H), 1.95-1.87 (m, 2H) ; MS (ES+) m/z 486.1 (M + 23) ° B· 1-( Diphenylmethyl)-3-(7-hydroxy-3,4_di-argon-2H. octadec-6-yl)·1,3-dihydro-2H- 143924-sp-20091127-1 -209- 201020257 嗓2. Synthesis of Ming according to the procedure as described in Preparation 4C, and insignificant changes, using 1-(diphenylfluorenyl)-3-trans-yl-3-(7-hydroxy-3,4-dihydro- 2H-pinene-6-yl)-1,3-dihydro-2Η-indol-2-one substituted 4-alkyl-1-(diphenylfluorenyl)_3_yl-3-(6- Hydroxy-2,3-dihydro-1-benzoin-5-yl)-1,3-dihydro-2H-indol-2-one to give 1-(diphenylmethyl)-3-( 7-Hydroxy-3,4-dihydro-2H- stilbene-6-yl)-1,3-dihydro-2-indole-2-one-2-one (81%) 'as pale yellow solid: mp 207- 2101 (hexane): 1H NMR (300 MHz, CDC13) (5 8.43 (br s, 1H), 7.37-7.22 (m, 11H), 7.09-7.03 (m, 2H), 6.99 (s, 1H), 6.58 (s, 1H), 6.56-6.50 (m, 1H), 6.48 (s, 1H), 5.05 (s, 1H), 4.15-4.08 (m, Φ 2H), 2.68-2.51 (m, 2H), 1.97-1.89 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 179.1, 155.4, 154.9, 143.4, 137.5, 137.4, 128.8, 128.7, 128.6, 128.5, 128.1, 127.9, 127.3, 125.9, 122.9, 115.8 , 114.6, 112.8, 106.7, 66.5, 58.8, 47.3, 24.4, 22.6; MS (ES+) m/z 448.1 (M + 1). Preparation 15 1-(Diphenylmethyl)-3-(8- mercapto- Synthesis of 3,4-dihydro-2H-1,5-benzodioxaerythritol-7-yl)-1,3-dihydro-2H-indol-2-one A. 1-(-Benzene Methyl)-3-carbyl-3-(8-carbyl-3,4-dihydro-2Η·1,5·benzo-dioxyanthene pentylene-7-yl)-1,3-di The synthesis of hydrogen-2Η-吲嗓-2·one is carried out according to the procedure described in Preparation 14Α, and irrelevant changes are applied, using 3,4-dihydro-2Η-benzo[b][l,4] Oxygen heptadecene-7-ol (Lange, J. et al., (2000), 53(1): 197-204) is substituted for indole-7-ol to obtain i-(diphenylmethyl)-3-hydroxy- 3-(8-hydroxy-3,4-dihydro-2H-1,5-benzo-dioxa nitrogen seven-potential _7_yl)-1,3-dihydro-2H-p5丨11 -2- Ketone (70%), light orange solid: n5-118 °C (diethyl ether / hexane); iH NMR (300 MHz, DMSO-d6) δ 9.25 (s, 1H), 143924-sp-20091127- 1 • 210 - (8) 201020257 7.42-7.29 (m, 11H), 6.98-6.80 (m, 4H), 6.58 (s, 1H), 6.30 (d, J = 7.8 Hz, 1H), 6.29 (s, 1H), 4.14-3.98 (m, 4H), 2.10-2.02 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 176.7, 150.9, 148.9, 143.3, 143.0, 138.2, 137.8, 132.5, 128.5, 128.4, 128.3, 128.1, 127.6, 127.4, 123.7, 122.5, 121.7, 120.2, 110.8, 107.7, 74.0, 70.71, 70.65, 57.3, 32.3; MS (ES+) m/z 502.1 (M + 23). Β·1·(diphenylmethyl)-3-(8-hydroxy·3,4-dihydro-2H-1,5-benzodioxyl-7-octenyl-7-yl)-1,3·2 The synthesis of hydrogen-2H-W-indol-2-one was carried out according to the procedure as described in Preparation 4C, and the insignificant change was carried out, © using quinonediyl)-3-carbyl-3-(8-hydroxy- 3,4-Dihydro-2H-1,5-benzodiazepine heptadec-7-yl)-1,3-dihydro-2H-indol-2-one substituted 4-chloro-1- (Diphenylmethyl)-3-carbyl-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1,3-dihydro-2H-indole-2 -ketone, 1-(diphenylhydrazinohydroxy-3,4-dihydrogen oxime benzodioxan-7-yl-7-yl)-1,3-dihydro-2H-indole-2- Ketone (91%) as an off-white powder · melting point 193-195 ° C (diethyl ether / hexane); 1 NMR (300 MHz, CDC13) (5 8.65 (br s, 1H), 7.39-7.27 (m, 9H ), 7.23-7.20 (m, 2H), 7.13-7.04 (m, 2H), 6.96 (s, 1H), φ 6.73 (s, 1H), 6.60 (s, 1H), 6.53-6.50 (m, 1H) , 5.09 (s, 1H), 4.25-3.99 (m, 4H), 2.22-2.06 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 178.9, 151.7, 151.6, 145.3, 143.3, 137.4, 137.1, 128.9 , 128.8, 128.6, 128.4, 128.2, 128.0, 126.5, 126.1, 123.1, 120.2 , 118.2, 112.9, 112.0, 71.0, 70.8, 58.9, 47.2, 32.3 ; MS (ES+) m/z 464.0 (M + 1) 〇 Preparation 16 1-(Diphenylmethyl)-3-(5-hydroxy-2 Synthesis of -methyl-1,3-benzoxazol-6-yl)-l,3-dihydro-2H-indol-2-one A. 1-(Diphenylmethyl)-3-hydroxy- 3-(5-hydroxy_2-methyl-1,3-benzoxazole_6_yl)_-211 - 143924-SP-20091127-1 201020257 1,3-dihydroindole-2- Synthesis of 2-mercapto-1'3-benzo-4-indole-5-ol (Fujita et al., 1982 (1982): 62-9) (10.3 g, 68.9 mmol) in anhydrous tetrahydrofuran (15 mL) In a cooled (〇°c) suspension, add isopropylmagnesium chloride (344 ml, 2.0 M solution in tetrahydrofuran, 68.9 mmol), stir the reaction mixture under 〇〇c for 5 hours, and add 1-Diphenylmethylindoline-2,3dione (18 8 g, 59.9 mmol) and anhydrous dichloromethane (15 mL). The reaction mixture was heated at reflux for 6 days and allowed to cool to ambient. The reaction mixture was diluted with a saturated aqueous solution of ammonium sulfate (200 ml) and ethyl acetate (2 mL) and separated. The aqueous phase was extracted with EtOAc (EtOAc (EtOAc)EtOAc. The crude product was purified by column chromatography eluting with hexane / ethyl acetate (3/1) followed by hexane/ethyl acetate to give bis(diphenylmethyl)-3-hydroxy-3- ( 5-hydroxyindenyl-1,3-benzoxazole_6-yl) 4,3 dihydrogen_condition_indol-2-one (3.10 g, 10%) 'as an off-white solid: 1 hnmr (3〇〇 Application, CDC13) 5 8.41 (br s, 1H), 7.63-7.60 (m, 2H), 7.47-7.32 (m, 10H), 7.15 (s, 1H), 7.04-6.96 (m, 1H), 6.96-6.88 (m, 1H), 6.87 (d, J = 9.0 Hz, 1H), 6.41 # (d7.8 Hz, 1H), 4.58 (br s,1H), 2.44 (s, 3H); MS (ES+) m/ z 445.2 (M-17). Β· 1-(Diphenylmethyl)-o-yl 2—methyl.u_benzoic acid _6·yl H,3 dihydro-2H-p5丨嗓-2·net synthesis according to preparation 1B The procedure described, and insignificantly changing, using 1-(diphenylmethyl)-3-hydroxy-3-yl (5-hydroxy-2-indenyl-13-benzoxazol-6-yl)-1,3- Dihydro-2H-indole-2-ketone replaces 3-hydroxyl (5hydroxy-2-indolyl-indole, 3 benzoxazol-6-yl)-1,3-dihydro-2H-indole_2 -ketone, obtain (diphenylmethyl)_3 (5_ 143924-sp-20091127-1 212 (S) 201020257 hydroxy-2-methyl-1,3-benzoxazol-6-yl)-1,3_ Dihydro-2H-W-indol-2-one (87%) was obtained as a colorless solid: MS (ESI) m/z 447.4 (M+l). Preparation 17 7-[1-(Diphenylindenyl)-2-keto-2,3-dihydro-1H-indol-3-yl]-6-hydroxy-4-methyl-2H-1,4 Synthesis of Stupid and Indole-3(4H)-ketone A. 7-[1-(Diphenylindenyl)-3.hydroxy-2-keto-2,3-dihydro-1H-indole_3 · Synthesis of -6-hydroxy-4-methyl·2Η-1,4·benzoxan-3(4Η)-ketone according to the procedure described in Preparation 14Α, and performing irrelevant changes, ® Replacement of hydrazine with 6-hydroxy-4-methyl-2-indole-benzo[b][l,4]indole-3(4Η)-one (Loudon and Ogg, / &amp; c., 1955: 739-743) -7-Alcohol, 7-[1-(diphenylmethyl)_3_hydroxy-2-keto-2,3-dihydro-1Η-indol-3-yl]-6-hydroxy- 4-indenyl -2Η-1,4-benzoindole-3(4Η)-one (27%) as an off-white solid: 1H NMR (300 ΜΗζ, DMSO-d6) δ 9.44 (s, 1 Η), 7.46-7.25 (m , 11H), 7.01-6.77 (m, 4H), 6.68 (s, 1H), 6.43 (s, 1H), 6.38-6.27 (m, 1H), 4.60 (s, 2H), 3.19 (s, 3H); MS (ES-) m/z 491.5 (M-1). Β ΉΗ ΉΗ ΉΗ 苯 苯 ) 酮 酮 酮 酮 酮 , 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Synthesis of 3(4Η)-net in 7-[1-(diphenylmethyl)yltransyl-2-keto-2,3-dihydro-exe_ruthenyl]_6_hydroxy-4-methyl -2Η-1,4-benzopyrene _3(4Η)-class (4.0 g, 8.1 mmol) in trifluoroacetic acid (1.8 ml, 24.4 mmol), triethyl decane (3.9 ml, 24.4 mmol) and the reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was concentrated in vacuo, and the crude material was purified by column chromatography using ethyl acetate (1 〇 to 1 〇〇% gradient) in hexane to give 7-[1-(diphenylhydrazine). Base)_2_keto-2,3_dihydro_1Η啕哚_3•yl]_卜hydroxy 曱 143924-sp-20091127-l -213- 201020257 base-2H-1,4-stup -3(4H)- Brewing I (2.66 g, 71%), as an off-white solid. · lU NMR (300 MHz, DMSO-d6) δ 9.53 (s, 1 Η), 7.44-7.28 (m, 10H), 6.99- 6.95 (m, 3H), 6.89-6.84 (m, 2H), 6.54 (s, 1H), 6.40 (m, 1H), 4.90 (s, 1H), 4.57 (s, 2H), 3.21 (s, 3H) ; MS (ES+) m/z 477.0 (M + 1). Preparation 18 6-[l-(Diphenylmethyl)-2-keto-2,3-dihydro-1H-indol-3-yl]-7-hydroxy-4-indolyl-2H-1,4 Synthesis of benzoindole-3(4H)-one A. Synthesis of 7-hydroxy-4-methyl-2Η-1,4·benzoindole-3(4H)-indole in 7-amino-4 -Methyl-2H-M-benzopyrone-3(4H)-one (10.0 g, 56 mmol) in water (80 mL) cooled ((TC) solution, concentrated sulfuric acid (17) After stirring for 10 minutes at 0 ° C, a solution of sodium nitrite (4.1 g, 59 mmol) in water (1 mL) was added dropwise. After stirring for 5 hours, under reflux The reaction mixture was added dropwise to a solution of copper sulfate (50 g) in water (3 mL). Once the addition was completed, the reaction mixture was cooled to ambient temperature &&lt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> And drying under high vacuum to give 7-hydroxy-4-methyl-2H-1,4- And sorghum-3(4H)-one (3_22 g, 32%) as a tan solid: 1H NMR (300 MHz, DMSO-d6) &lt;5 9.40 (s, 1H), 6.95 (d, J = 8.7 Hz, 1H), 6.45 (dd, J = 8.7, 2.6 Hz, 1H), 6.40 (d, J = 2.6 Hz, 1H), 4.56 (s, 2H), 3.21 (s, 3H) ; MS (ES+) m /z 180.1 (M + 1) Β·6-[l-(Diphenylmethyl)-3-hydroxy.2·keto-2,3·dihydro-1H-W 哚_3-yl]-7 · Synthesis of mercapto-4-methyl-2H-1,4-benzobenzazole_3(4H)-indole 143924-sp-20091127-l •214- 201020257 according to the procedure as described in Preparation 16A, and is carried out Inconsistent change, replacement of 2-mercapto-l,3-benzo-4-indol-5-ol with 7-hydroxy-4-methyl-2H-1,4-benzoxan-3(4Η)-one , 6-[H Diphenylmethyl)_3_transyl-2-keto-2,3-dihydro-1H-indol-3-yl]-7-pyridyl-4-methyl-2H-1 , 4-Benzoindole-3(4H)-one (74%), as an off-white solid: 1H NMR (300 MHz, DMSO-d6) 5 9.54 (s, 1H), 7.55 (s, 1H), 7.42- 7.30 (m, 10H), 6.99-6.94 (m, 2H), 6.88 (s, 1H), 6.86-6.80 (m, 1H), 6.71 (s, 1H), 6.35-6.30 (m, 2H), 4.61 ( s, 2H), 3.32 (s, 3H) ; MS (ES+) m/z 475.0 (M-17).鲁C·6-[H Diphenylmethyl)-2-keto-2,3·dihydro_1H-啕哚-3·yl]-7-hydroxy-4-methyl-2Η·1,4· Synthesis of benzoindole-3(4Η)·ketone•fee according to the procedure described in the preparation of 17Β' and performing an insignificant change, using 6-[1-(di-m-methyl)-3-carbyl- 2-keto-2,3-dihydro-1H-indol-3-yl]-7-hydroxy-4-methyl-2H-1,4-benzoindole-3(4H)-one substitution 7 -(1-Diphenylmethyl_3_yl-2-onedihydrochoindan-3-yl)-6-hydroxy-4-methyl-2H-benzo[b][l,4]〃 No.-3(4H)-ketone' gives 6-[1-(diphenylmethyl)-2-keto-2,3-dihydro-iH-p-p--3-indolyl]-7- Transphenyl-4-methyl-2H-1,4-benzoindole-3(4H)-one (65%) as amorphous solid: MS (ES+) m/z 477.4 (M+l) . Preparation of 19 6-[H-Butyl)-2-keto-2,3-dihydro-1Η-Θ布-3-yl]-5-pyridyl-3-yl-l-1,3-benzene弁吟°Sit-2(3H)-嗣Synthesis Α· 5·{[Third-butyl(dimethyl)alkyl]oxy}·13. Synthesis of benzoxazole-2(3H)•嗣5-(yl)-1,3-benzoxanthene-2(3H)-one (dirty et al., /.(iv)c/^ 2〇〇2 (67): 7424-7428) (1.00 g ' 6.6 mmol) In the solution of anhydrous n,N-dimethylformamide 143924-SP-20091127-1 -215- 201020257 (10 ml), imidazole (0.54 g, 7.9 mmol) was added, followed by gas- Third-butyl dimethyl decane (U0 g, 7-3 mmol). The reaction mixture was stirred at ambient temperature for 16 hours and concentrated in vacuo. The crude product was purified by column chromatography using ethyl acetate (hexane to 5% gradient) to give 5-{[tris-butyl (dimethyl) succinyl] [, 3, benzoxazole-2(3Η)-one (1.53 g, 87%), as colorless solid: iHNMR (300MHz, CDCl3) (5 9.04 (br s, 1H), 7.04 (d, J = 8.3 Hz, 1H), 6.60-6.53 (m, 2H), 0.98 (s, 9H), 〇.19(s,6H) 〇B· 5-{[Second-butyl (monomethyl) dream Synthesis of ketone]oxy}-3-methyl-1,3-benzopyrene _ 2(3H)-net in 5-{[tri-butyl(dimethyl)-stone base] Ethyl iodide, 3·benzoxazole_2(3H)_ _ (1.45 g, 5.4 mmol) cooled in anhydrous n,N-dimercaptocaramine (1 mL) (( TC) solution, sodium hydride (0.26 g, 6 % dispersion in mineral oil, 6.6 mmol) was added. The reaction mixture was stirred under hydrazine for 15 minutes, followed by the addition of methyl iodide (1.0 mL, 16 mM). The reaction mixture was stirred at ambient temperature for 16 hours' and diluted with water (20 mL) and ethyl acetate (2 mL). The liquid phase was separated and ethyl acetate (2 X 20 mL) The aqueous phase was extracted. The combined organic solution was washed with water (5×20 mL) and brine (2×20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Purification by chromatography, using ethyl acetate (〇 to 25% gradient) in hexanes to give 5-{[tris-butyl(dimethyl)oxalyl]oxy}whenyl- _13 Benzo-p-salt-2(3H)-one (1.26 g, 83%) as a pale yellow solid: 1H NMR (300 MHz, CDC13) 5 7.02 (d, J = 8.6 Hz, 1H), 6.55 (dd, J = 8.6, 2.4 Hz, 1H), 6.44 (d, J = 2.4 Hz, 1H), 3.35 (s, 3H), 0.99 (s, 9H), 0.20 (s, 6H). 143924-sp-20091127-1 216 (S) 201020257 C. Synthesis of 5-hydroxy-3-methyl-1,3-benzoxazole-2(3H)-indole from 5-{[tri-butyl(dimethyl)-osmectane a thiophene-3-methyl dj·benzoxazole-2(3H)-one (1.20 g, 4.3 mmol) in a cooled (〇°C) solution in anhydrous tetrahydrofuran (15 mL) Add tetrahydro-tetra-butyl (drops, 1 M 'in tetrahydrofuran t, 4.7 mmol) dropwise. The reaction mixture was stirred at ambient temperature for 16 hours. Concentrated in vacuo. Ethyl acetate (10 ml) and 1M hydrochloric acid solution (20 ml) were added to the residue, and the resulting suspension was shaken for 5 minutes. The product was collected by vacuum filtration, washed with ethyl acetate (1 EtOAc), air dried, and dried under high vacuum to give 5-hydroxy-m-methyl-l-benzoxazole-2 (3H)- Ketone (0.47 g, 67%) in pink solid: ihnmr

(300 MHz, DMSO-d6) 5 9.52 (br s,1H), 7.09 (d, J = 8.6 Hz, 1H), 6.62 (d, J = 2.4 Hz, 1H), 6.47 (dd, J = 8.6, 2.4 Hz, 1H), 3.27 (s, 3H) ; MS (ES-) m/z 164.2 (M -1). D·6·[1 Benzylmethyl)·3_经基.2_keto_2,3_二式_m•咖朵_3•基]5•hydroxy-3-methyl-1,3 - Synthesis of benzoxazole-2 (3H)- Brewing I φ According to the procedure as described in Preparation 16A, and with irrelevant changes, 5-hydroxy-3-methyl-1,3-indole is used. Azole 2(3Η)-ketone is substituted for 2_methyl_13_ benzoxazole-5-ol to obtain 6-[1-(diphenylmethyl)_3_hydroxy-2-keto-2,3_ Dihydro_ιη-indol-3-yl]-5-hydroxy-3-methyl-1,3-benzoxazole-2(3Η)-one (66%) as a pink solid: MS (ES+ ) m/z 461.1 (Μ -17). E. 6-[1 benzoquinone)_2-keto-2,3-di-argon·Xun ♦3_yl]_5•hydroxy_3_methyl_1'3·benzo 1^嗤· Synthesis of 2(3Η)__ι according to the procedure as described in Preparation 9Β, and using an insignificant change, using 6-[1-(diphenylfluorenyl) hydroxy hydroxy ketone ketone 2 3 dihydrol hydrazine哚冬基]j

143924-sp-20091127-1 -217- 201020257 Hydroxy-3-indolyl-1,3-benzoxazol-2(3H)-one is substituted for 3-hydroxyl (6-carbyl-3-methyl-1, 2-Benzoisoxazole _5_yl) 4_(4-methoxyindenyl) 4,3_dihydro_2H_吲哚! Ketone to obtain 6-[1-(diphenylmethyl)-2-keto-2,3-dihydro-1H-indoleyl-3-methyl-1,3-benzoxazole·2 ( 3Η)-ketone (98%), yellow amorphous solid: Ms (ES+) m/z 463.4 (Μ + 1). Preparation of 20 5-[1-(-phenylhydranyl)-2-keto-2,3-dihydro-1Η-indol-3-yl]-6-pyridyl-3·A disease-U-benzo Synthesis of carbazole-2(3Η)-ketone Α·第三[Terbutyl(dimethyl)decyl]oxy}-3_methyl_13_benzoxazol-2(3Η)-嗣之Synthesis in a solution of 6-hydroxy-1,3-benzoxazole-2(3Η)-one (4.9 g, 32 mmol) in anhydrous hydrazine, hydrazine-dimethylformamide (40 ml) Add imidazole (26 g, 39 mmol) with gas-third-butyl dimethyl decane (54 g, % mmol). The reaction mixture was stirred at ambient temperature for 16 h and diluted with EtOAc (EtOAc). The resulting suspension was filtered and the fluid was concentrated in vacuo. The residue was dissolved in anhydrous hydrazine, hydrazine-dimercaptocaramine (5 mL) and cooled to o. To this solution, sodium hydride (1.6 g, 60% dispersion in mineral oil &apos; 39 mmol) was added and the reaction mixture was spoiled for 15 minutes. Iododecane (6 &gt; 1 mL, 97 mmol) was added and the reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated in vacuo and EtOAcqqqqqqqq The liquid phase was separated and the aqueous phase was extracted with ethyl acetate (2×100 mL). The combined organics were washed with water (2×100 mL) and brine The crude product was purified by column chromatography 143924-sp-20091127-1 -218-201020257 using hexane/acetic acid ethyl acetate (5/1) to give 6-{[tri-butyl(didecyl) Amidoxime]oxy}-3-methyl-1,3-benzoxazole-2(3H)-one (6.55 g, 72%) as a colorless solid.··············· 6.79-6.72 (m, 2H), 6.69-6.64 (m, 1H), 3.36 (s, 3H), 0.98 (s, 9H), 0, 17 (s, 6H). Synthesis of Β·6·hydroxy-3-methyl·1,3·benzoxazole-2(3H)-one According to the procedure as described in Preparation 19C, and performing irrelevant changes, use 6-{[ Tertiary-butyl(dimethyl)oxalyl]oxydi-3-methylbenzopyrene-salt-2(3H)-one substituted 5-{[tri-butyl(dimethyl)shi Alkyl]oxy}methyl®-1,3-benzopyrene ° sitting _2(3H)-ketone' to obtain 6-hydroxy-3-methyl-1,3-benzoxazole-2 (3H )-ketone (99%) as a tan solid: iHNMR (3 〇〇 MHz, DMS 〇 _d6) 5 9.5 〇 s, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.75 (d, J = 2.1 Hz, 1H), 6.62 (dd, J = 8.4, 2.1

Hz, 1H), 3.27 (s, 3H) ; MS (ES-) m/z 164.2 (M -1). C. 5-[l_(diphenylindenyl)·3_hydroxy·2.keto-2,3-dihydro-m啕哚_3_yl]_6_hydroxy-3-pyridyl·1,3- Synthesis of benzoxazole. 2(3H)·ketone According to the procedure as described in Preparation 15A, and irrelevant changes are made, φ uses 6-hydroxy-3-methylbenzoxazole-2(3H)- Ketane Substituted 2-Mercapto-1,3-benzoxan-5-ol' to give 5-[1-(diphenylmethyl)_3_transyl-2-keto-2,3-dihydro-1H - anthracene-3-yl]-6-hydroxy-3-methyl-1,3-benzoxazole·2(3Η)-one (46%) as an off-white solid: 4 NMR (300 MHz, DMSO- D6) 5 9.62 (br s,1Η), 7.64 (s,1Η), 7.47-7.25 (m, 10H), 7.06-6.71 (m, 5H), 6.65 (s, 1H), 6.30 (d, J = 7.9 Hz, 1H), 3.38 (s, 3H) ; MS (ES+) m/z 479.1 (M + 1). D·5·[1_(diphenylmethyl)-2-yl.2,3-dihydro.ih-W 哚-3-yl]-6-yl--3-methyl-1,3-benzene And the synthesis of the sputum saliva-2 (3H)-steel according to the procedure as described in Preparation 17B, and the implementation of the insignificant change, 143924-sp-20091127-1 •219- 201020257 using 5-[1-(diphenyl) Methyl)-3-yl-2-keto-2,3-dihydro-1H-indole-3-yl]_6_hydroxy-3-indolyl-1,3-benzazole-2 (3H )-keto-substituted 7-(1-di-p-methyl-3-pyridyl-2-ketoindan-3-yl)-6-hydroxy-4-indolyl-2H-benzo[b][ i,4]呤耕-3(4H)-ketone' obtains 5-[1-(diphenylmethyl)-2-keto-2,3_dihydro_m吲哚_3_yl]-6-hydroxyl -3-Methyl-1,3-benzoxazole-2(3H)-one (73%), m.p. Preparation 21 7-Chloro-1-(diphenylhydrazinyl)-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)q,3_dihydro-2H-,5h Synthesis of adol-2-one A. Synthesis of 7-yl-1-(diphenylmethyl)-ih-rakistan-2,3-dione according to the procedure as described in Preparation 4A, and the implementation is irrelevant The change, using 7-alkyl-1H-indole-2,3-dione to replace 4-methyl-1H-indole-2,3-dione, 7-chloro-1-(diphenyl) Base)_1H_ 哚 哚_2,3_dione (38%), orange solid: melting point 172-173 ° C (hexane / ethyl acetate); 1 η nmr (3 〇〇 ship, DMS (&gt ;d6 ) (5 7.71-7.60 (m, 2H), 7.36-7.27 (m, 11H), 7.22-7.17 (m, 1H). Β·7· gas-based-1-(monophenylmethyl).3· Synthesis of 2,3-dihydrobenzoyl via a group of _3_(6_carbyl-2,}dihydrobenzophthalazin-5-yl)-1,3-dihydro-2ΗΜ哚_2-one Furan_6-alcohol (52 g, 38 mmol) in anhydrous tetrahydrofuran (25 ml) cooled ((rc) solution, isopropyl magnesium hydride (2.1 ml, in tetrahydrofuran) PCT solution, 42 mM. The resulting suspension was stirred at TC for 5 hours, followed by a small addition of 7 _ gas base (two曱)) 4H-(tetra)-2,3-dione (3) gram, 15.5 mmol. The reaction mixture was stirred at ambient temperature for 3 hr and concentrated in vacuo. Ethyl acetate (0% to 50% gradient), 143924-SO-20091127-1 201020257 gives 7-chloro-1-(diphenylmethyl)-3-hydroxy-3-(6-hydroxy-2 ,3-dihydro-1-benzofuran-5-yl)-1,3-dihydro-2H-indol-2-one (7.12 g, 95%), m.m. DMSO-d6) δ 9.43 (s, 1Η), 7.56-7.18 (m, 13H), 6.99- 6.86 (m, 2H), 6.60 (s, 1H), 6.08 (s, 1H), 4.56 (t, J = 8.6 Hz, 2H), 3.10 (t, J = 8.6 Hz, 2H) C. 7-Chloro-1-(diphenylmethyl)_3_(6-hydroxy·2,3·dihydro·i•benzo Synthesis of 1,3-diaza-2Η·&lt;»5丨嗓-2-嗣 according to the procedure as described in Preparation 4C, and performing irrelevant changes, ® using a small 7-gas base (diphenylhydrazinyl)-3-hydroxy-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1,3-dihydro-2Η-啕哚-2- Ketone replacement 4-chloro-based benzyl benzyl) _3_hydroxy-3-(6-hydroxy-2,3-dihydro-1-benzopyran-5), ), 3 _Dihydro 2 Η-Θ丨哚-2-ketone 'obtained 7-yl-1-(diphenylhydrazino) hydroxyl-2,3 dihydrogen + benzofuran _5_ yl)-1,3-di Hydrogen-2Η-indol-2-one (64%) as a colorless solid: iH NMR (300 MHz, DMSO-d6) δ 9.53 (s, 1 Η), 7.44-7.20 (m, 13H), 7.01-6.91 ( m, 2H), 6.22 (s' 1H), 4, 82 (s' 1H), 4.48 (t, J = 8.5 Hz, 2H), 3.03 (t, J = 8.5 Hz, 2H). Preparation 22 1-(Diphenylmethyl)-7-fluoro-3-hydroxy-3-(6-hydroxy-2,3-dihydrobenzobenzopyran-5-yl)-1,3-dihydro-2H- Synthesis of 4丨嗓-2-ketone A. Synthesis of 1-(diphenylfluorenyl)-7-fluoroyl-hydrazine-&lt;咮-2,3-dione according to the procedure as described in Preparation 4Α, and Inconsistent changes were made using 7-fluoro-1Η-沔丨ρ多-2,3-dione (Kalia, Ν. et al., /. Afei/. CTiem. 2007; 50: 21-39) - gas-based-1H-indole 2,3-dione, obtaining μ(diphenylfluorenyl)_7_fluoroyl-1Η-indole-2,3-dione (56%) as an orange solid: 1Η Wake (3〇〇ΜΗζ, CDC13) (5 7.52-7.47 (m, 1H), 7.42-7.30 (m, 10H), 7.29-7.21 (m, 1H), 7.13- 143924-sp-20091127-1 •221 - 201020257 7.05 (m,1H), 6.99 (br s,1H) ; MS (ES+) m/z 353.9 (Μ + 23). Β· 1-(Diphenylmethyl)-7-fluoro-3-hydroxyl Synthesis of -3-(6-hydroxy-2,3-dihydro-1_benzofuran-5-yl)-1,3·dihydro-2Η·Θ卜-2-one according to Preparation 21 The procedure described, the insignificant change, the replacement of 7-chloro-1-(diphenylmethyl) with 1-(diphenylindenyl)-7-fluoro-1Η-吲哚_2,3-dione -1Η' -2,3-dione, obtaining μ(diphenylmethyl)_7-fluoro group hydroxy_3_(dihydroxy-2,3-dihydro-1-benzofuran_5_ylindene) dihydro-2Η呻哚 ketone (99%), as a colorless solid, m.p., 121-122 ° C (hexane / ethyl acetate); iH NMR (3 〇〇MHz, DMSO-^) δ 9.44 (s, 1H), 7.62 (s, 1H), 7.42-7.29 (m, 10H), 6.98 (s, ® 1H), 6.93-6.87 (m, 2H), 6.78-6.65 (m, 2H), 6.11 (s, 1H), 4.52 ( t, J = 8.7 Hz, 2H)' 3.14 (t, J = 8.6 Hz, 2H); MS (ES+) m/z 467.9 (M + 1). Preparation of 23 H-diphenylmethyl)-4-fluoro- Synthesis of 3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-7-indenyl-13-oxo-2Η-μ丨嗦-2-one A. 1-( Synthesis of diphenylhydrazinyl)-4-fluoro-7-methyl-1Η-吲哚_2,3dione According to the procedure described in Preparation 4Α, and irrelevant changes are made, ^ Μ 4-| l ^ -7-f ^ ^ .2,3-- m (Cassebaum, J. Prakt. Chem. ^ (1960) 12 . 91-92) Displacement of 4-gas-based _ιη·4 哚_2,3_2 The ketone gives i (diphenylhydrazinyl H-f-yl-7-mercapto-1HH2,3-dione (45%) as a brown solid: ι NMR (300 MHz, CDC13) (5 7.38-7.27 (m, 11H), 6.81 (s, 1H), 6.71 (dd, J = 8.3' 8.3 H z, 1H), 2.27 (s, 3H); MS (ES+) m/z 367.7 (M + 23). Β· 1-(Diphenylmethyl)·4·fluoroyl·3—hydroxyl (6-hydroxy-2,3 dihydro q•benzofuran-5-yl)·7·methyl·1,3- The synthesis of dihydro 2 ΐι·4 dyedone is carried out according to the order as described in Preparation 21Β, and the irrelevant changes are performed, • 222· 143924-sp-20091127-l

201020257 Substituting 1-(diphenylfluorenyl)-4-fluoro-7-methyl-1H-indole-2,3-dione for μ(di-p-methyl)&gt;7-chloro-1Η-4哚-2,3-dione to give 1-(diphenylmethyl)-4-fluoro-3-hydroxy-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl )-7-Mercapto-1,3-dihydro-2-indole-2-one (56%) as a colorless solid: iHNMRQOOMHz 'CDCls) δ 8.88 (s, 1H), 7.40-7.09 (m, 11H) ), 6.85-6.79 (m, 2H), 6.60 (br s, 1H), 6.38 (s, 1H), 4.54 (m, 2H), 4.08 (s, 1H), 3.13-2.94 (m, 2H), 2.28 (br s, 3H) ; MS (ES+) m/z 503.8 (M+23).

C· 1-(Diphenylmethyl)-4-fluoro-3-(6-carbyl-2,3-dihydro-1·benzoin-5-yl)·7_methyl-1,3 - Synthesis of dinitro-2H-H5丨嗓-2-indole according to the procedure as described in Preparation 4C, and insignificantly changing, using 1-(diphenylmethyl)-4-y! -3-(6-carbamic-2,3-dihydro-1-benzopyran-5-yl)-7-fluorenyl-1,3-dihydro-2H-indol-2-one replacement 4 -yl-1-(diphenylfluorenyl)-3-carbyl-3-(6-hydroxy-2,3-dihydrobenzobenzofuran-5-yl)indole-3-dihydro-2H_吲哚2-ketone, 1-(diphenylmethyl)_4•fluoroyl_3_(6-hydroxy-2,3·dihydrobenzobenzopyran-5-yl)-7-mercapto-1,3- Dihydro 2H-indole-2-ketone (61%) ' is a colorless solid: Ms (ES+) m/z 465.7 (M+l). Preparation of 24 H5-bromo-2-hydroxyphenyl)-indole_{[5·(trifluoromethyl)furan-2-yl]methyl}-a•dihydro-2H-indole-2-one 3-(5-&gt;Smoke·2·Phenyl) is a small ((5(trifluoromethyl) 2)yl)dihydroindol-2-one synthesized according to Prepare the procedure for the 犹 叮 叮 , , , , , , , , , , , , 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备 制备2-yl]methyl}-1H-p5| p-2-3 3,- ata ~ _substitution 1-(diphenylmethyl)-1Η-吲哚-2,3-di 143924-sp-20091127-l - 223- 201020257 ketone to give 3-(5-bromo-2-hydroxyphenyl)-3-hydroxy-1-((5-(trifluoromethyl)furan-2-yl)indolyl) dihydro-p-bow Indole-2-one (62%) as a white solid: iHNMR (300 MHz, CDC13) δ 8.73 (s, 1H), 7.49-7.37 (m, 2H), 7.31 (dd, J = 8.8, 2.6 Hz, 1H), 7.25-7.17 (m, 1H), 7.03 (d, J = 7.9 Hz, 1H), 6.93 (d, J = 2.3 Hz, 1H), 6.86 (d, J = 8.5 Hz, 1H), 6.74- 6.68 (m, 1H), 6.38-6.32 (m, 1H), 5.00-4.81 (m, 2H), 4.09 (s, 1H) ; MS (ES+) m/z 449.9 (M -17), 451.3 (M - 17) B. 3-(5-Bromo-2-hydroxyphenyl)-1·{[5-( The synthesis of fluoromethyl)pyran-2-yl]methyl}·1,3-diaza·2Η-ρ5丨'• 嗣-2-嗣 is carried out according to the procedure described in Preparation 17Β, and irrelevant changes are performed. Using 3-(5-bromo-2-hydroxyphenyl)-3-carbyl-1-((5-(trifluoromethyl)oxy-2-yl)methyl)indoline-2 -keto-substituted 7-[1-(diphenylmethyl)-3-yl-2-ylidene-2,3-dihydro-indole-indole-3-yl]-6-carbyl-4- Mercapto-2Η-1,4-benzo-p-'well--3(4Η)-one, 3-(5-bromo-2-hydroxyphenyl)-1-{[5-(trifluoroanthracene) (1) NMR (300 MHz, CDC13) 5 8.78 (br s, 1H), 7.44-7.36 (m, 1H), 7.36-7.19 (m, 3H), 7.08 (d, J = 7.9 Hz, 1H), 6.99 (d, J = 2.3 Hz, 1H), 6.94 (d, J = 8.5 Hz, 1H), 6.73-6.68 (m, 1H), 6.37-6.32 (m, 1H), 5.10 (s, 1H), 5.00-4.85 (m, 2H) ; MS (ES+) m/z 452.0 ( M + 1) 0 Preparation 25 8-(7-Hydroxy-2,3-dihydrobenzoxan]dioxyterpene _6_yl)_6-isopentyl_6H_ pyrazolo[5,4-e Synthesis of H|哚-7(8H)-ketone VIII.6-(3-methylbutyl)-611-[1,3]11-pyrazole[5,4-curry-7,8- Diketone Synthesis at ambient temperature '6H-pyrazolo[5,4_e]吲哚_7,8-dione (2.83 g, 13.9 mmol) in anhydrous tetrahydrofuran (12 mL) with N,N-didecyl A carbonated planer (23 g, 70 mmol) was added to the stirred solution of the mixture of methotrexate 143924-SP-20091127-1 -224- 201020257 (80 ml). The dark purple mixture was stirred for 5 hours, followed by the addition of 1-bromo-3-indenylbutane (4.15 mL &apos; 35.0 mmol). The mixture was stirred at ambient temperature for 16 hours' and poured into 8 ml of ice water and extracted with ethyl acetate. The orange solution was filtered through Shixia, and dehydrated and dried with sulfuric acid, and filtered. The filtrate was concentrated to dryness in vacuo and the residue was crystallised eluted eluted eluted eluted eluted : 1H NMR (300 MHz, CDC13) (5 9.36 (s, 1H), 8.38 (d, J = 8.6 Hz, 1H), 7.37 (d, J = 8.6 Hz, 1H), 3.77-3.69 (m, 2H ), 1.74-1.58 (m, 1H), 1.57-1.47 (m, 2H), 0.94 (d, J = 6.5 Hz, 6H). Β·8·hydroxy-8-(7·经基·2,3- Dihydro·1,4-benzodioxanthene·6_yl)_6.(3·decylbutyl)-6,8·dihydro-711-[1,3&gt; Synthesis of 4-eH哚-7·ketone According to the procedure as described in Preparation 6A, and irrelevant changes were made, 2,3-dihydrobenzo[b][l,4]dioxene terpene was used. 6-Alcohol replaces 3,4-diphenol, and 6-(3-mercaptobutyl)-6Η-[1,3]oxezo[5,4-e]吲嗓-7,8- Diketone replacement of φ 1_(diphenylfluorenyl)·1Η_吲哚-2,3-dione to give 8-hydroxy-8-(7-trans-based-2,3-dihydro-1,4-stupid Dioxodecenyl)_6_(3_mercaptobutyl)_6 8_dihydrogen^^嗤[5,4-e]indole-7-one (46%) : 4 NMR (300 MHz , CDC13) δ 9.00 (s, 1Η), 8.80 (s, 1H), 7.96 (d, J = 8.5 Hz, 1H) , 7.27 (s, 1H), 7.20 (d, J = 8.5 Hz, 1H), 6.55 (s, 1H), 4.15 (s, 4H), 3.81-3.59 (m, 2H), 1.79-1.55 (m, 1H) ), 1.56-1.42 (m, 2H), 0.93 (d, J = 6.6 Hz, 6H); MS (ES+) m/z 427.0 (M + 1). C· 8-(7-base 2,3 -dihydro-1,4-benzodioxene _6•yl)_6_(3·methylbutyl)-6,8-dihydro-7Η·[1,3]ρ-saxazole[s , 4-e]吲哚-7· ketone synthesis according to the procedure as described in Preparation 12B, and the implementation of irrelevant changes,

143924-SP-20091127-1 -225· 201020257 The use of 8-carbyl-8-(7-hydroxy-2,3-dioxabenzo[b][l,4]dioxolene-6-yl) _6_Isoamyl-6H-pyrazolo[5,4-eH哚-7(8H)-_substituted 1-(diphenylfluorenyl)_3_ylamino-3-(2-hydroxy-4-oxirane -i,3-dihydro-2H-indol-2-one, obtaining 8-(7-hydroxy-2,3-dihydro-1,4-benzodioxene-6-yl) _6_(3_methylbutyl)_6,8-dihydro-7H-[1,3&gt;- oxazolo[5,4-eH 哚-7-one (93%): MS (ES+) m/z 411.0 (M + 1). Preparation 26 8-(6-Hydroxy-2,3-dihydro-1-benzofuran-5-yl)-6-{[5-(trifluoromethyl) succinyl-2-yl] fluorenyl}- Synthesis of 2,3,6,8-tetrahydro-7Η-[1,4]dioxolysine[2,3-fH丨哚-7-one ❹ A· 6-{[5-(trifluoro Methyl)anthracene·2·yl]fluorenyl}·2,3-dihydro-6Η·[1,4]dioxoisen[2,3·ί]吲哚-7,8-dione Synthesis at ambient temperature in 2,3-dihydro-6Η-[1,4]dioxolene [2,3&lt;ΗΙ哚-7,8-dione (Lackey and Stembach, S; yni) /ie also 1993: 993-997) (3.08 g, 15.0 mmol) Adding hydrogenation (0.9 g, 60%) in a stirred solution in anhydrous N,N-dimercaptocaramine (150 ml) In mineral oil, 22.5 millimoles). The dark purple mixture was stirred for 20 minutes, then 2-(bromomethyl)-5-(trifluoromethyl)pyran (3.80 g, 16.5 mmol) was added in one portion. The dark solution was stirred at ambient temperature for 1 hour and concentrated in vacuo to dryness. The residue was mixed with water (150 ml) and stirred. The fine orange precipitate was filtered off and dried to give 6-{[5-(trifluoromethyl)furan-2-yl]indolyl}-2,3-dihydro-6H-[1,4] Oxadecene [2,3-fH 哚-7,8-dione (4.13 g, 78%): iHNMR (300 MHz, CDC13) (5 7.18 (s, 1H), 6.76-6.73 (m, 1H) ), 6.48 (s, 1H), 6.45-6.40 (m, 1H), 4.85 (s, 2H), 4.42-4.32 (m, 2H), 4.28-4.20 (m, 2H) ° B· 8-hydroxy-8 -(6-hydroxy-2,3-dihydrobenzobenzopyran-5-yl)-6-{[5-(trifluoromethyl) 143924-SO-20091127-1 -226- 201020257 吱-2- Synthesis of hydrazino}-2,3,6,8-tetrahydro-711-[1,4]dioxene decene [2,3-€1 1111 -7-嗣 according to Preparation 6A The procedure described, and insignificant changes, the replacement of 3,4-dioxan with 2,3-dihydrobenzofuran-6-ol, and the use of 6-{[5-(trifluoromethyl)anthracene喃-2-yl]methyl}-2,3-dihydro-6H-[1,4]dioxolynene [2,3〇〇哚-7,8-dione substituted 1-(diphenyl) Methyl)-1Η-吲哚-2,3-dione, which gives 8-hydroxy-8-(6-carboxy-2,3-dihydrobenzoindole-5-yl)-6-((5- (trifluoromethyl) pfutong-2-yl)methyl)-6,8-dihydro-2H-[1,4]dioxolynene[2,3-f]indole-7 ( 3H)- Ketone (76%): ❹ 1H NMR (300 MHz, CDC13) δ 9.08 (s, 1 Η), 7.07 (s, 1H), 6.74-6.68 (m, 1H), 6.64 (s, 1H), 6.52 (s, 1H), 6.48 (s, 1H), 6.36-6.32 (m, 1H), 4.84 (dd, J = 48.7, 16.3 Hz, 2H), 4.53 (t, J = 8.7 Hz, 2H), 4.32-4.20 (m , 4H), 4.16 (s, 1H), 3.08-2.94 (m, 2H); MS (ES+) m/z 471.9 (M -17). C· 8-(6-hydroxy-2,3-dihydro- 1·benzofuran-5-yl)·6-{[5-(trifluoromethyl y-pyran-2-yl) fluorenyl}·2,3,6,8-tetrahydro-7Η·[1, 4] Synthesis of dioxerecane [2,3.f]吲哚-7-oxime 0 at 0 C in 8-hydroxy-8-(6-hydroxy-2,3-dihydrobenzofuran _5-yl(trifluoromethyl)furan-2-yl)methyl)-6,8-dihydro-2-indole-[1,4]dioxolynene [2,3-fH哚-7 ( 3 Η)-ketone (1.81 g, 3.70 mmol) in a solution of dichloromethane (5 mL) was added triethyl decane (6. liters) and trifluoroacetic acid (1 liters). The resulting mixture was stirred at (TC for 2 hours and concentrated to dryness in vacuo to give 8-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-6-? [5_(Trifluoromethyl)furan-2-yl]indenyl}_2,3,6,8-tetrahydro-7Η-[1,4]dioxanthene dilute [2,3-fH -7 -ketone (100%, 97%): MS (ES+) m/Z 473.9 (M + l). Preparation 27 143924-sp-2009l 127-1 201020257 8-(6-Phase-2,3- Dihydrobenzopyran-5-yl)-6-(((R)-tetrahydroindole.South-2-yl)indenyl)-6,8-dihydro-2Η-[1,4]dioxo Synthesis of ruthenium [2,3-f]indole-7(3Η)-one A·6-[(2R)-tetrahydrofuran-2-ylmethyl].2,3-dihydro·6Η-[ 1,4] Dioxo sulphate [2,3-fH丨哚·7,8. Diketone synthesis at ambient temperature 'in 2Η-[1,4] dioxygen ore and [2,3 -f]M丨嗓-7,8(3Η,6Η)_dione (2.05g '1〇·〇 mmol) in anhydrous ν,Ν-dimercaptocaramine (1 ml) After the mixture was mixed, carbonic acid (4.4 g, 12.0 mmol) was added. The dark mixture was stirred for 1 hour, followed by a portion of 4-(methyl)-(-)-(tetrahydrofuran-2-yl)- Ester (3.07 g, 12.0 mmol) and iodide Potassium (0.66 g, 4.0 mmol). The dark mixture was stirred at 7 rc for 16 h. The mixture was poured into 5% HCl (3 mL) and extracted with ethyl acetate. Dehydrated with magnesium sulfate, filtered, and evaporated. The residue was purified by flash column chromatography using ethyl acetate ethyl acetate (3 〇 to %% gradient) to give 6-[(2R) -w Hydrofuran-2-ylmethyl]-2,3-dihydrodioxolynene [2,3-fH丨哚-7,8-dione (0.59 g, 20%): MS (ES+ m/z 290.2 (M+1) Β·8_hydroxy-8·(6-hydroxy·2,3·dihydro.1.benzofuran·5.)_6_[(2R)_tetrahydrofuran Synthesis of β-oxo-2-ylmethyl]-2,3,6,8·tetrahydro-711-[1,4]dioxolynene [2,3·η吲哚-7· ketone according to Prepare the procedure described in 6Α, and perform irrelevant changes, use 2,3- 虱 吱嗔 and 吱嗔-6-ol to replace 3,4-dimethyl, and use 6-[(2R)-tetrahydro Indole-2-ylmethyl]-2,3-dihydro-6H-[1,4]dioxanthene-inden-7,8-dione substituted 1-(diphenylmethyl)_ih- Indole-2,3-dione to give 8-hydroxy-8-(6-hydroxy-2,3-dihydrobenzobenzofuran-5-yl) 6_[(211)_tetrahydrofuran-2-ylmethyl]_ 143924-sp-20091127-1 -228- 201020257 2,3,6,8-tetrahydro-7Η:-[1,4] Dioxane hydrazine [2,3-f]indole-7-one: Rf 0.45 (ethyl acetate / hexane, 1/1); MS (ES+) m/z 408.1 -17). C· 8-(6-hydroxy·2,3·dihydro-1-benzofuran·5·yl)-6-[(2R)-tetrahydrofuran-2-ylmethyl]-2,3,6,8 · Synthesis of tetrahydro-7 Η-[1,4]dioxo-enoxa[2,3-f]ind-7-one according to the procedure as described in Preparation 12B, and with irrelevant changes, used 8-hydroxy-8-(6-hydroxy-2,3-dihydrobenzofuran-5-yl)-6-(((R)-tetrahydrofuran-2-yl)indolyl)-6,8-dihydro -2H-[1,4] Dioxoline dilute [2,3-fp? Budu-7(3H)-ketooxime substituted quinodiphenyl)-3-hydroxy-3-(2-trans 4-(6-hydroxy-2,3-dihydro-1-benzofuran-5)-[4-oxophenyl)-1,3-dihydro-2H-indol-2-one -6-[(2R)-tetrahydrofuran-2-ylmethyl]-2,3,6,8-tetrahydro-7H-[1,4]dioxolynene [2,3-f&gt;5丨哚-1-m (76%) : 1H NMR (300 MHz, CDC13) δ 9.27-9.07 (m, 1Η), 6.90-6.81 (m, 1H), 6.74 (s, 1H), 6.72-6.68 (m, 1H), 6.53 (s, 1H), 4.99-4.89 (m, 1H), 4.62-4.45 (m, 2H), 4.38-4.08 (m, 5H), 3.94-3.57 (m, 4H), 3.18-2.89 ( m, 2H), 2.06-1.93 (m, 1H), 1.93-1.78 (m, 2H), 1.72-1.55 (m, 1H); MS (ES+) m/z 410.0 (M + 1). 28 Preparation 28 8-(7-Hydroxy-2,3-dihydro-1,4-benzodioxanthene-6_yl)_6_丨[5_(trifluoromethyl) benzo-2-yl ]Methyl}-2,3,6,8-tetrahydro- melon-like] Dioxoindole[2,3__哚-7-one synthesis A· 8-hydroxy-8-(7-hydroxy- 2,3_Dihydrobenzo[b][1,4]dioxanthene·6-yl)·6_((5-(trifluoromethyl)-pyran-2-yl)methyl)·6 , 8 dihydro.215^4]dioxanthene [2,3-fH丨哚-7 (3Η), the synthesis according to the procedure as described in Preparation 6Α, and the implementation of irrelevant changes, 143924- SO-20091127-1 201020257 Replacement of 3,4-dioxan with 2,3-dihydrobenzoindole]][1,4]dioxanthene-6-ol, and use of 6-{[5-( Trifluoromethyl)-pyran-2-yl]methyl}-2,3-dihydro-6H-[1,4]dioxolynene[2,3-f]indole-7,8- Diketone replacement of quinodiphenyl)-1Η-啕哚-2,3-dione' affords 8-hydroxy-8-(7-hydroxy-2,3-dihydrobenzo[b][l,4] Dioxetene-6-yl)-6-((5-(trifluoromethyl)pyran-2-yl)indolyl-6,8-dihydro-2H-[1,4]dioxo圜 圜 并 [2,3-fH 哚-7(3H)-one (80%): 1H NMR (300 MHz, CDC13) δ 8.78 (s, 1 Η), 7.07-6.97 (m, 1H), 6.71- 6.65 (m, 1H), 6.60-6.5 5 (m, 1H), 6.51-6.47 (m, 1H), 6.40-6.35 (m, 1H), 6.31-6.25 (m, 1H), 4.89-4.69 (m, 2H), 434-4.04 (m, 9H MS (ES+) m/z 487.9 (M-17). ❹ Β 8-(7-Hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-6-{[5-(trifluoromethyl)pyran-2 -Based on the synthesis of methyl}-2,3,6,8-tetrahydro-7Η·[1,4]dioxanthene [2,3-f] budo-7-indole according to Preparation 26C The procedure described and 'insignificantly changed, using 8-carbyl-8-(7- mercapto-2,3-dihydrobenzo[b][l,4]dioxane _6_yl -6-((5-(Trifluoromethyl)pyran-2-yl)methyl)-6,8-dihydro-2H-[1,4]dioxane dilute [2,3~ 〇Μ丨11 -7(3H)-ketones are substituted by 8-yl-8-(6-carbyl-2,3-dihydrobenzopyran-5-yl)-6-((5-(three) Fluoromethyl)pyran-2-yl)indenyl)-6,8-dihydro-2H-[1,4]dioxo® cedarene[2,34吲哚-7(3H)-one, Obtaining 8-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-6-{[5-(trifluoromethyl)pyran-2-yl Methyl b 2,3,6,8-four winds _7H-[l,4]-oxo-indole and [2,3-f]'I5丨嗓-7-鲷 (89%): 1H NMR ( 300 MHz, CDCI3) δ 8.46 (s, 1H), 6.86 (s, 1H), 6.69 (d, J = 2.9 Hz, 1H), 6.61 (s, 1H), 6.54 (s, 1H), 6.45 (s, 1H), 6.29 (d, J = 2.9 Hz, 1H), 4.95 (s, 1H), 4.89-4.74 (m, 2H), 4.31-4.06 (m, 8H) Preparation 29 143924-sp-20091127-l •230· 201020257 3-(7-^-based icylmethyl_3,4·dihydro-2H-l,4-benzin _6_yl)_ι_{[5_ Synthesis of (trifluoromethyl)pyran-2-yl]methyl H,3_dihydro-2 private 吲哚_2-ketone trifluoroacetate A. 4-methyl-3,4-dihydro· 2Η·Benzene[b][l,4] No.7·Alcohol synthesis in 7-bromo-4-methyl-3,4-dihydro-2H-1,4-benzopyrene (9 〇%, 10·4 gram, 41.0 mmol.) In a solution of _78 〇c in tetrahydrofuran (70 ml), a solution of n-butyl hydride (1.4 M in a hospital) was added under nitrogen. 32 ml, 45 mmol, and the resulting suspension was stirred at _78 ° C for 35 minutes. Tridecyl borate (6 ml, 54 mmol) was then added dropwise and the clear solution ® was stirred at -78 °C for 25 minutes and at ambient temperature for 16 hours. The reaction was cooled to 0 ° C and aqueous hydrogen peroxide (2 2 mL, 35%, 95 mmol) was slowly added. The resulting mixture was placed in a crucible. Stir under the arm for 1 minute and at ambient temperature for 5 hours. The insoluble material was removed by filtration, and the filter cake was washed with ethyl acetate. The filtrate was concentrated under reduced pressure and the residue was crystalljjjjjjjjj The layers were separated and the organic solution was extracted with water (2 X 50 mL). The combined aqueous solution was neutralized to pH ~ 6-7' with 5M sodium hydroxide and extracted with ethyl acetate (3 X 1 mL). 9 of this organic solution was washed with brine (200 ml), dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by flash column chromatography using hexane/ethyl acetate (2:1) to give 4-methyl-3,4-diaza-2H-benzo[b][l,4 ] 噚-7-ol (6.04 g, 89%), as a light brown solid: mp. 84. (: (ether); 4 NMR (300 MHz, CDC13) δ 6.59 (d, J = 9.0 Hz, 1H), 6.40-6.28 (m, 2H), 5.42 (br s, 1H), 4.30 (dd, J = 4.2, 4.2 Hz, 2H), 3.19-3.09 (m, 2H), 2.80 (s, 3H); 13 C NMR (75 MHz, CDC13) 5 149.1, 145.6, 130.5, 114.7, 108.0, 104.1, 65.3, 49.8, 40.1 ; MS (ES+) m/z 166.1 (M+ 1). 143924-sp-20091127-1 •231 - 201020257 Β· 3-Hydroxy-3-(7-hydroxy-4·decyl _3,4-dihydro -2H-1,4-Benzene alpha tillage _6·基)_ι_ {[5·(二敦曱基户失味.2-基]曱基}·ι,3·Dihydro-2Η-Θ丨嗓·2-network synthesis according to the procedure described in Preparation 21Β, and the implementation of irrelevant changes, using 4-mercapto-3,4-dihydro-2!^-stup [13][1,4 ] 哼 7-alcohol replaces 2,3-dihydrobenzofuran-6-ol, and 1-((5-(trifluoromethyl)pyran-2-yl)indenyl) indoline is used. 2'3-dione replacement of 7_gas-based small (diphenylmethyl)_m啕哚_2,3 diketone to obtain 3-hydroxy-3-(7-hydroxy-4-indolyl-3,4-di Hydrogen-2Η-1,4-benzoxan-6-yl)-1-{[5-(difluoromethyl)-butan-2-yl]methyl}4,3-dihydro-2Η-吲Indole-2-one (56%), a colorless powder Melting point 184-186 ° C (diethyl ether / hexanes); 1H NMR (300 MHz, DMSO-d6) </ RTI> 8.63 (s, 1H), 7.24-7.18 (m, 2H), 7.13 (s, 1H), 7.00- 6.90 (m, 3H), 6.59 (d, J = 3.3 Hz, 1H), 6.50 (s, 1H), 6.03 (s, 1H), 4.99 (s, 2H), 4.20 (t, J = 4.1 Hz, 2H ), 3.14-3.09 (m, 2H), 2.80 (s, 3H); 13C NMR (75 MHz, DMSO-d6) (5 176.8, 153.8, 145.8, 144.1, 142.8, 139.3 (q, J = 42 Hz), 132.7, 128.9, 128.5, 123.7, 122.2, 119.6, 119.1 (q, J = 266 Hz), 114.1, 112.3, 109.1, 108.3, 103.1, 74.7, 64.9, 49.2, 394, 36.4; MS (ES+) m/z 461.2 (M + 1). C· 3-(7-Hydroxy-4-indolyl-3,4-dihydro·2Η_1,4-benzoindole-6-yl)-l-{[5-(trifluoromethyl)-ranane- 2-Based]methyl}-1,3·dihydro-2HW哚-2-one trifluoroacetic acid salt® Synthesized in triethyldecane (1.1 ml '6.9 mmol) in trifluoroacetic acid (6.5 ml) In the cooled (0 ° C) solution, slowly add 3_hydroxy_3_(7-hydroxy-4-mercapto-3,4-dihydro-2H-1,4-benzene) as a solid. 445 各 ))) 445-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one (ι·〇〇克, 2.18 mmol) . The resulting brown solution was warmed to reflux and stirred under nitrogen for 2 h. The reaction was allowed to cool and the solvent was removed under reduced pressure. The residue was precipitated from ethyl acetate 143924-sp-20091127-1 -232· 201020257 ester/hexane and collected by filtration to give 3-(7-hydroxy-4-methyl-3,4-dihydro-2H -1,4-benzoindole-6-yl)-H[5-(trifluoromethyl)pyran-2-yl]methyl H,3-dihydro-2H-indol-2-one Fluoroacetate (1.09 g, 90%), light gray powder: mp 143-148 ° C (hexanes); 1H NMR (300 MHz, DMSO-d6) &lt;5 8.98 (br s, 2H), 7.24- 7.15 (m, 2H), 7.05-6.92 (m, 3H), 6.62 (s, 1H), 6.61 (s, 1H), 6.22 (s, 1H), 5.08 (d, J = 16.7 Hz, 1H), 5.01 (d, J = 16.7 Hz, 1H), 4.78 (s, 1H), 4.27-4.21 (m, 2H), 3.23-3.17 (m, 2H), 2.77 (s, 3H) ; MS (ES+) m/z 445.2 (M + 1) 0 Preparation 30 3-(7-Hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoindole-6-yl)-l-[(2R) Synthesis of -tetrahydrofuran-2-ylmethyl]-1,3-dihydro-2H-indol-2-one trifluoroacetate A. 1-[(2R)-tetrahydrofuran-2-ylmethyl]-1H - Synthesis of indole-2,3-dione according to the procedure as described in Preparation 4A, and irrelevant changes, replacement of 4-gas-based hydrazine with hydrazine, and use of 4-mercaptobenzene sulfonate Acid (R)-(tetrahydrofuran-2-yl Yue bromo ester substituted diphenylmethane, obtained tetrahydrofuran-2-ylmethyl] -1H- indole-2,3-dione (47%) as a thick red oil:! h NMR (300 MHz, CDC13) &lt;5 7.60-7.54 (m, 2H), 7.14-7.07 (m, 2H), 4.25-4.17 (m, 1H), 3.92-3.82 (m, 2H), 3.78-3.69 (m, 2H), 2.13-2.02 (m, 1H), 1.98-1.85 (m, 2H), 1.74-1.65 (m, 1H); 1 3C NMR (75 MHz, CDC13) 5 183.5, 158.8, 151.8, 138.5 , 125.3, 123.8, 117.7, 111.7, 68.4, 44.7, 29.3, 25.8; MS (ES+) m/z 232.1 (M+l). B. 3-Hydroxy-3_(7-carbyl-4·methyl-3,4-dihydro-2-indole-1,4·benzo, acenaphthyl)-1-[(2R)-tetrahydrofuran Synthesis of -2-ylmethyl]·ι,3. Dihydro-2Η-indol-2-one According to the procedure described in Preparation 13Α, and irrelevant changes, 143924-sp-20091127-1 -233- 201020257 Substituting 4-mercapto-3,4-dihydro-2H-benzo[b][l,4], cultivating -7-alcohol for hydra-7-ol, and using 1-[(2R) )-tetrahydrofuran-2-ylindenyl]-1H-indole-2,3-dione displaces 1-(diphenylmethyl)indoline-2,3-dione to give 3-hydroxy-3- (7-Hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoindole_6-yl)-l-[(2R)-tetrahydrofuran-2-ylindenyl]-1 , 3-dihydro-2H-indol-2-one (91%), as pale grey solid: 1H NMR (300 MHz, CDC13) (I 隹 enantiomer) (5 8.94 (s, 0.4H) , 8.80 (s, 0.6H), 7.52-7.48 (m, 1H), 7.41-7.34 (m, 1H), 7.20-7.08 (m, 2H), 6.52 (s, 1H), 6.16 (s, 1H), 4.51 (s, 〇.4H), 4.44 (s, 0.6H), 4.29-4.17 (m, 3H), 3.90-3.64 (m, 4H), 3.17-2.99 (m, 2H), 2·58 (s, 3H), 2.04-1.78 (m, 3H), 1.74-1.60 (m, 1H); 13 C NMR (diastereomer) (75 MHz, CDC13) &lt;5 179.4, 179.2, 149.4, 149.3, 146.2, 143.2, 143.0, 130.2, 130.1, 129.8, 129.6, 125.9, 125.7, 123.6, 123.5, 117.6, 112.7, 112.4' 110.4' 110.3, 107.4, 79.3, 79.2 , 76.9, 76.7, 68.3, 68.2, 65.3, 49.5, 44.7, 44·6, 39.5, 29.3, 29.1,25·7, 25.6 ; MS (ES+) m/z 419.1 (M + 23). C. 3-( 7-By-based 4-4-mercapto-3,4-dihydro-2H-1,4-benzoxan-6-yl)-l-[(2R)·tetrahydrofuran-2-ylindenyl]·1 Synthesis of 3-dihydro-2H.indole-2-one trifluoroacetate salt. According to the procedure described in Preparation 12, and irrelevant changes were made, 3-amino-3-(7-trans-based) was used. 4-methyl-3,4-dihydro-2-indole-1,4-benzoxanyl _ _6-yl) small [(2R)-tetrahydrofuran-2-ylmethyl]-1,3-dihydro-2Η -Indol-2-one substituted μ(dimethylene)-3-carboxy-3-(2-hydroxy-4-methoxyphenyl)-1,3-dihydro 2Η-cologne, obtained 3-(7- mercapto-4-mercapto-3,4-dihydro-2Η-1,4-benzoindole _6_yl) small [(2R)_四风咬喃-2-基甲Base]-1,3-«一风-2H-p5| p-wood-2-indole acetate (93%) as a pink solid: iH NMR (300 MHz, DMSO-d6) (diastereomeric Structure) accounted for 9.07 (br s, 1H), 7.24-7.17 (m, 1H), 7.12-7.05 (m, 1H), 7.01-6.88 (m, 2H), 6.63, 6.57 (s, 1H), 6.24, 6.21 (s, 1H ), 4.71, 4.68 (s, 1H), 4.32-4 11 (m 3H) 143924-sp-20091127-1 •234- 201020257 3.85-3.58 (m, 4H), 3.25-3.14 (m, 2H), 2.79, 2.75 (s, 3H), 1.98-1.61 (m, 4H); MS (ES+) m/z 381.1 (M + 1) 31 Preparation 31 3-(6-Hydroxy-4-methyl-3,4-dihydro -2H-1,4-benzoxanthene-7-yl) Synthesis of small [(2R)_tetrahydrofuran-2-ylindenyl]-1,3-dihydro-2H-indole-2-one. 3·Hydroxy-3-(6-hydroxy-4_methyl.3,4-dihydro·2Η-1,4-benzoxanth-7-yl) small [(2R)-tetrazolfuran-2- Synthesis of dimethyl-2-indole, fluorenone according to the procedure described in Preparation 14Α, and insignificant changes, using 4-mercapto-3,4-indan-2-indole-benzo [^[1,4]11ρ井-6- leaven (McMurtrey, KD et al., 7. Org. (1970), 35(12): 4252-3) Displacement of 咣-7-ol, and use 1 -[(2R)-tetrahydrofuran-2-ylmethyl]-1H-indole-2,3-dione displaces 1-(dihydroindenyl) indoline-2,3-dione to give 3- Hydroxy-3-(6-hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoxan-7-yl) -l-[(2R)-Tetrahydrofuran-2-ylindenyl]-1,3-dihydro-2H-indol-2-one (92%) as a light brown solid: 1H NMR (300 MHz , CDC13 ) δ 9.21 (d, J = 13.6 Hz, 1H), 7.46 (d, J = 7.2 Hz, 1H), 7.36 (dd, J = 7.8, 7.8 Hz, 1H), 7.17 (dd, J = 7.5, 7.2 Hz, 1H), 7.09 (d, J = 7.8 Hz, 1H), 6.40 (s, 1H), 6.18 (s, 1H), 4.25-4.06 (m, 3H), 3.87-3.63 (m, 4H), 3.27-3.17 (m, 2H), 2.87 (s, 3H), 2.02-1.74 (m, 3H), 1.71-1.57 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 179.8, 179.7, 151.54, 151.52, 143.1, 143.0, 138.0, 137.4, 130.12, 130.10, 129.32, 129.29, 126.1, 126.0, 123.8, 114.8, 114.6, 113.1, 113.0, 110.4, 1103, 103.5, 79.11, 79.06, 76.9, 76.7, 68.32, 68.26, 64.6, 48.9, 44.6, 38.5, 29.3, 29.1, 25.7, 25.6; MS (ES+) m/z 418.9 (M + 23). 3-(6-Hydroxy-4-methyl-3,4-dihydro-2Η-1,4-benzoindole-7-yl)-1-[(2R)-tetrahydrofuran-2-yl Synthesis of benzyl]-1,3-dihydro-2H-W哚-2· ketone 143924-SP-20091127-1 -235- 201020257 in triethyl hydrazine (1.3 ml '8.2 mmol) in trifluoroacetic acid (3 ml) in a cooled (0 C) solution - dropwise addition of 3-yl-3-(6-pyridyl-4-methyl-3,4-dihydro-2H-1,4- this And ν»井-7-基)-l_[(2R)_tetrahydro ol 0 South _2 yl fluorenyl]-1,3-dihydro-2H-indol-2-one (1.04 g, 2.62 Millol) A solution in two gas (3 ml). The resulting solution was allowed to warm to reflux and stirred under air for 90 minutes. Once cooled, the solvent was immediately removed under reduced pressure to give 3-(6-hydroxy-4-methyl-3,4-dihydro-2H-1,4-benzoindole _7·yl) small [(2R)_Tetrahydrofuran-2-ylmethyl]-1,3-dihydro-2H-V?indole-2-one trifluoroacetate as pale brown foam: MS (ES+) m/z 381.0 (M+1). Preparation 32 3-(7-Hydroxy-4H-U- benzodioxanthene) H_[(2R),hydrofuran-2-ylindenyl]-1,3-dihydro-2H-4哚-2 - Synthesis of ketones A. 3-Phase-based 3-(7.-Pyano- 4Η·1,3-benzodioxanthene-6·yl) Small __Tetrahydro hydrazine-2-yl fluorenyl Synthesis of -1,3-dihydro.2Η-ι^丨嗓_2_ Ming according to the procedure described in Preparation 6Α, and performing irrelevant changes, using 4Η-benzo[d][l,3]二^陆圜# _7• Alcohol substitution from dimethyl 35, and using (RH-((tetramethylene-2-yl) fluorenyl) dihydro quinone _2,3_dione to replace ι (diphenylmethyl) ΗΗ-射-2'3-二_ 'Get 3 基基娜基基·4Η4,3 benzodioxanthene -6-ylindole-_-tetrahydroanthracene 2_ylmethyl hydrazine, 3 _二氮细+朵^ _2%), as a colorless solid: Ms(ES+)m/z366 2(M _ 17) B. 3-(7•hydroxy·4Η-1,3-benzo-open-oxygen Synthesis and implementation of irreversible changes in the synthesis and implementation of tert-en-6.yl)-l-[(2R)·hydrofuran-2-ylmethyl]-1,3-dihydro-2H-W哚1鲖·Oxygen-wife-female-6-base)-l-[(2R)-four

3-Hydroxy-3-(7-hydroxy-4Η-1,3- 并 143924-sp-20091127-1 ~ 236 * 201020257 Hydrazine-2-ylmethyl) was used according to the procedure described in Preparation 9Β] -1,3-Dihydro-2H-indole-2-one replaces 3-hydroxy-3-(6-hydroxy-3-methyl-1,2-benzisoindole-5-yl)-1- (4-曱oxybenzyldichloro-2H呻嗓-2-one' obtained 3-(7-transalkyl-4H-1,3-benzodioxanthene-6-yl) small [(2R )_ Tetrahydrofuran-2-ylmethyl]-1,3-dihydro-2H-indole-2-one (84%) as a colorless solid: MS (ES+) m/z 368.2 (M+ l) Preparation 33 Synthesis of 4-methylphenyl acid (S)-2-(thyloxydecyloxy)propyl ester at (2S)-2-[(yanooxy)曱 at 〇°C氡基] propyl alcohol (Banfl丄 et al, y © kiss. Wm. (1984) '49: 3784-90) (11.40 g, 0.058 mol) in dichloromethane (50 ml) with bites (20 Gasoline p-phenylsulfonate (11.0 g, 0.057 mol) was added to the stirred solution in ML. The reaction mixture was stirred at ambient temperature for 20 hours 'diluted with ethyl acetate' and taken with water, 5% Hydrochloric acid solution, water and brine washing 'dehydrated with anhydrous sodium sulfate, and dried over. Concentration. Purification of the residue by EtOAc EtOAc EtOAc EtOAc CDC13) (5 7.77 (d, J = 8.3 Hz, 2H), 7.36-7.25 (m, 7H), 4.71 (s, 2H), 4.59- 4.48 (m, 2H), 4.02-3.93 (m, 3H), 2.41 (s, 3H), 1'19-Ul (m, 3H). Preparation 34 2-(&gt; odoryl fluorenyl)-7-fluorobenzobenzopyran. A. 7-Fluorobenzoxp Synthesis of ethyl-2-carboxybenzate 3-fluoro-2-hydroxybenzaldehyde (5 g, 357 mmol), potassium carbonate (9 85 g, 71.4 mmol) and ethyl bromide a mixture of ester (4 3 mL, 39 3 mmol) in N,N-dimethylformamide (70 mL), EtOAc And extracted with ethyl acetate (3 χ 15 〇 ml) 143924-sp-20091127-1 • 237- 201020257. The combined organic solution was washed with brine (15 ml), dried over anhydrous sulphuric acid, filtered, Concentration in vacuo. Purify the residue by column chromatography (hexane/ethyl acetate, 49/1~&gt; 9/1) to give 7-fluorobenzene. Ethyl furocarboxylate (3.86 g, 52%) with yellow oil: 1H nmr (3 〇〇 MHz, CDCl3) ά 7.56-7.54 (m, 1H), 7.47-7.42 (m, 1H), 7.28- 7.14 (m, 2H), 4.46 (q, J = 7.1

Hz, 2H), 1.43 (t, J = 7.1 Hz, 3H). Synthesis of (7·fluorobenzobenzopyran-2-yl)methanol at 0C in ethyl 4-fluorobenzofuran-2-carboxylate (370 g, 17 8 mmol) in tetrahydrofuran ( In a stirred solution of 70 ml), lithium aluminum hydride (6.7 ml, 2 〇Μ solution in tetrahydrofuran, 13 3 mmol) was added. The mixture was stirred at 0 C for 0.5 hour' and solid sodium sulfate decahydrate (15.0 g) was slowly added portionwise. The mixture was stirred for 1 min at 〇t: and 30 knives at ambient temperature. The solid was taken up and washed with ethyl acetate (3 mL). The combined filtrate was washed with brine (15 mL EtOAc) The residue was purified by column chromatography (hexane/ethyl acetate, 7/1 - 4/1) to give (7-fluorobenzofuranyl)methanol (24 g, 81%) as colorless. Solid: iHNMR (300 MHz, CDC13) (5 7.34-7.29 (m, _ 1H), 7.19-7.10 (m, 1H), 7.06-6.98 (m, 1H), 6.73-6.69 (m, 1H), 4. 4.78 (m, 2H), 2.07-2.01 (m, 1H); MS (ES+) m/z 167.1 (M + 1). C. 2·(Mosylmethyl). Synthesis of 7-fluorobenzofuran (7-Fluorobenzofuran-2-yl)methanol (1.38 g, 8.31 mmol), tetrabromomethane (4.41 g, 13.3 mmol) and triphenylphosphine (2.61 g, 9 97) Mixture of methylene chloride in di-methane (42 ml), stir at 〇 °c for 2 hrs, and dilute to dryness in vacuo. Purify the residue by column chromatography (hexane/acetic acid 143924- Sp-20091127-1 -238 - 201020257 Ethyl vinegar '49/1) to give 2-(bromohydrazino)-7-fluorobenzofuran (1.85 g, 97%) as colorless solid: iHNMR (300MHz , CDC13) 5 7.34-7.29 (m,1H), 7.20-7.12 (πι,1H), 7.10-7.02 (m,1H),6.82-6.77 (m,1H), 4.60 (s,2H). Preparation 35 4 -methylbenzenesulfonic acid (R Synthesis of _(i,4-dioxoindole-2-yl)methyl ester to (S)-(l,4-oxoindol-2-yl)methylate (Kim, HY et al., Mei L. (2005), 15: 3207-11) (2.02 g, 17.1 mmol) and pyridine (14 ml '173 mmol) in di-methane (11 mL) cooled (〇〇c The gasified p-toluenesulfonate (3.85 g, 20.2 mmol) was added to the solution. The reaction was stirred at 0 ° C for 20 minutes and at ambient temperature for an additional 15 5 hours. The methane (1 ml) was diluted and washed successively with hydrochloric acid (1 mL, 2M), water (50 mL) and brine (50 mL). Concentration under pressure. Purify the residue by flash column chromatography using hexane/ethyl acetate (2:1 to 3:2) to give 4-indole as acid (R)-(l,4- Monooxan-2-yl) 曱g (3.40 g, 73%), as colorless solids: m.p. 53-54. 〇 (dichloromethane); 1 η NMR (300 MHz, CDC13) &lt;5 7.79 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 4.02 (dd, J = 10.8, 5.4 Hz, 1H), 3.95 (dd, J = 10.5, 4.5 Hz, 1H), 3.82-3.50 (m, 6H), 3.35 (dd, J = 11.6, 9.8 Hz, 1H), 2,45 (s,3H) ; MS (ES+) m/z 295.0 (M + 23). Preparation 36 4-Methylbenzenesulfonic acid (s)-(i,4-dioxaindole-2-yl) decyl ester was synthesized according to the procedure as described in Preparation 35, and the insignificant changes were used ( R)-(l,4-dioxoindole-2-yl)methanol (Kim, Η·γ et al., et al., C7zm. Leii. (2005), 15: 3207-11) Replacement (3)_(1,4 _ Dioxanthene-2-yl) decyl alcohol, 143924-SP-20091127-1 -239· 201020257 Obtained (S)-(l,4-dioxoindolin-2-yl) 4-methylbenzenesulfonic acid Methyl ester (79%) as colorless solid: m.p. 53-55 ° C (di-methane); 1H NMR (300 MHz, CDC13) (5 7.78 (d, J = 8.1 Hz, 2H), 7.34 (d, J = 8.1 Hz, 2H), 4.01 (dd, J = 10.5, 5.4 Hz, 1H), 3.94 (dd, J = 10.4, 4.7 Hz, 1H), 3.82-3.50 (m, 6H), 3.34 (dd, J = 11.2, 10.1 Hz, 1H), 2.44 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 145.2, 132.7, 130.0, 128.1, 72.4, 68.8, 67.8, 66.5, 66.4, 21.8 ; MS (ES+) m /z 294.9 (M + 23) Preparation 37 7-Bromo-3-(6-hydroxy-1,3-benzodioxanthene-5_yl)_3_(hydroxydecyl argon-2H-M丨Synthesis of 嗓-2-嗣 A. 7-Bromo 3-hydroxy_3_(6-hydroxy-1,3-benzodioxol-5-yl)-1, Synthesis of 3-dihydro-2H-*»?丨嗓-2· ketone in 〇°C and under nitrogen, in sesame alcohol (7·32 g, 531 mmol) in anhydrous tetrahydrofuran (150 ml) Adding isopropylmagnesium chloride solution (2.0 M in tetrahydrofuran, 3αι ml, 6〇2 mmol), stir the reaction mixture at 0 C for 30 minutes, then add 7-bromo hydrazine ( 8 克, 35.4 mmol. The suspension was stirred at ambient temperature for 16 hours. The reaction mixture was diluted with saturated aqueous ammonium chloride (300 mL) and ethyl acetate (25 mL) and separated. The aqueous phase was extracted with ethyl acetate (2 mL) and the combined organics were washed with brine (1 mL), dried over anhydrous sodium sulfate, and evaporated and evaporated. Developed, filtered, and dried under reduced pressure to give 7-bromo-3_hydroxy-3 (6-hydroxybenzodioxol-5-ylindole, 3·dihydro·2Η_吲哚Butanone (9 8 g, 77%) as a pale yellow solid: 4 NMR (10) MHz, DMS 〇 _d6) 5 1 () 64 (s, 1 Η), 9 i8 h 1H), 7.33 (dd, J = 7.8 , 1. 4 Hz, 1H), 7.21 (s, lH), 6.84-6.75 (m, 2H), 6.54 (s, 143924-sp-20091127-1 201020257 1H), 6.21 (s, 1H), 5.92 (dd, J = 6.1, 0.8 Hz, 2H) ; MS (ES+) m/z 363.8 (M + 1), 365.8 (M + 1). Synthesis of 8.7-bromo-3-(6-yl-l-1,3-benzodioxolan-4-yl)-1,3-dihydro-211 oxime-2-one from 7-bromo 3--3-hydroxy-3-(6-hydroxy-1,3-benzodioxanthene-5-yl) is dihydro-2H-indol-2-one (9.50 g, 27.3 mmol) Triethyl decane (6.12 g, 528 mmol) was added at 0 ° C in a solution of trifluoroacetic acid (24 mL). The mixture was stirred at ambient temperature for 3 hours. The reaction was allowed to float by the addition of a mixture of hexane and diethyl ether (2.1, 3 (8) mL). The sediment was filtered and washed with a mixture of hexane and a mixture of domains (100 ml). The solid was dried under reduced pressure to give 7-bromo-3-(6-hydroxy-1,3-benzodioxanyl)-u-dihydro-2H- fluorenone (8.40 g '93 %) ' is an off-white powder: 1h NMR (300 MHz, DMS (M6;) δ 10.67 (s, 1H), 9.26 (s, 1H), 7.33-7.31 (m, 1H), 6.90-6.78 (m, 2H), 6.68 (s, 1H), 6.38 (s, 1H), 5.91 (d, J = 1.0 Hz, 2H), 4.75 (s, 1H) ; MS (ES+) m/z 347.9 (M + 1), 349.9 (M + 1) ❹ C· 7·溪基·3.(6-carbyl·1,3·benzodioxol-S-yl)-3-(methyl)·1,3· dihydrogen ·Synthesis of 2Η-ρ?丨嗓-2-one under 〇C's 7-enyl-3-(6-hydroxy-1,3-benzodioxol-5_yldihydro-2H Add NaOH (3 84 g, a mixture of fluoren-2-one (8.40 g ' 24.1 mmol), polyformaldehyde (2. 88 g, 96 〇 mmol) and water (80 ml). 96.0 mmol. The dark green solution was stirred for 4 hours. The mixture was acidified to pH 4 with EtOAc (3 mL) and extracted with ethyl acetate (3 x 1 liters). % vaporized ammonium solution (5 ml) washed with brine (50 ml) to dry Drying over sodium sulfate and concentrating 143924-sp-2009 1127-1 -241 - 201020257 to dryness in vacuo. The residue was taken in toluene (300 ml) to give an off-white precipitate. The precipitate was filtered and dried under reduced pressure. , obtaining 7_bromo groups (6_carbyl_u_benzino-oxo-5-yl)-3-(methyl-)-1,3-dihydrooxan-2-one (4.80 g) , 53%): 4 NMR (300 MHz, DMSO-d6) 5 10.48 (s, lH), 9.16 (S, 1H), 7.27 (dd, J = 8.0, 1.0 Hz, 1H), 7.01 (s, 1H) , 6.87-6.74 (m, 2H), 6.22 (s, 1H), 5.91 (s, 2H), 5.03 (br, 1H), 4.12 (d, J = l〇.〇Hz, 1H), 3.85 (d, J = i〇.〇Hz, 1H) ; MS (ES-) m/z 376 (M - 1), 378 (M -1). Preparation 38 3-[5-(yloxy)-2-hydroxybenzene Synthesis of H-[(5-Chlorosulfonyl)methyl]_3 (hydroxymethyl hydrazino)-1,3-dihydro-2H-M丨嗓-2-_ Α·3·[5· (Ethyloxy)·2-hydroxyphenyl]-indole-[(5·glycosyl porphinyl)methyl]hydroxy-1,3-dihydro-2Η-4bido·2·one The synthesis was carried out in a pale yellow solution of 4-(benzyloxy)phenol (9.01 g, 45. 〇 mmol) in anhydrous tetrahydrofuran (100.0 mL) at EtOAc. Propyl magnesium hydride (263 liters, 52.5 millimoles, 2 〇M solution in tetrahydrofuran) ^ The reaction solution was stirred for 0.5 hours, followed by the addition of ^(10)-gassulfimen-2-yl) sulfhydryl) Dihydro(9)indole-2,3-dione (8·31 g, 30. 〇 millimol). The reaction mixture was stirred at ambient temperature for 10 hours for 16 hours. The reaction was quenched by the addition of saturated aqueous ammonium sulphate (5 mL) and concentrated to dryness in vacuo. The residue was diluted with ethyl acetate (1 EtOAc), washed with EtOAc EtOAc (EtOAc (EtOAc) The filtrate was concentrated to dryness in the vacuum. The residue was purified by column chromatography using ethyl acetate to give 3-[5-(benzyloxy&gt; 2-hydroxyphenyl)-di-chloropyrimidin-2-yl)] Hydroxy-1,3-dihydro-2H-indole-2-one (4.90 g, 28%) as a colorless solid: melt 143924-sp-20091127-1 (S) -242- 201020257 point 174-175 °C; WNMR (300 MHz, CDC13) 5 8.45 (br,lH), 7.40-7,27 (m, 7H), 7.14 (dd, J = 7.5, 7.5 Hz, 1H), 6.92 (d, J = 2.9 Hz, 1H), 6.89 (s, 1H), 6.83 (d, J = 2.9 Hz, 1H), 6.79 (d, J = 3.7 Hz, 1H), 6.70 (d, J = 3.7 Hz, 1H), 6.43 ( d, J = 2.9 Hz, 1H), 4.86 (ABq, 2H), 4.84 (s, 2H) ; 13 C NMR (75 MHz, CDC13) δ 178.3, 152.6, 149.790, 141.7, 136.8, 135.8, 130.4, 130.1, 129.1, 128.6, 127.9, 127.6, 126.3, 126.2, 126.0, 125.9, 124.3, 120.2, 116.3, 114.4, 109.6, 79.1, 70.6, 39.2; MS (ES+) m/z 478.2 (M -1), 476.2 (M - 1). Β·3·[5·(narrow oxy)-2-hydroxyphenyl]_1·[(5-avidyl sulfonyl-2-yl)methyl]-1,3·diindole® -2Η-峋哚Synthesis of 2-ketone to 3-[5-(benzyloxy)-2-hydroxyphenyl]-indole-[(5-chloro-2-pyrimenyl)methyl]-3-yl-1 , 3-Dihydro-2Η-indol-2-one (4.90 g, 10.3 mmol) in a solution of di-methane (100.0 mL) - trifluoroacetic acid (12.9 g, 113.2 mmol) Triethyl decane (13.2 g, 113.2 mmol) was stirred at ambient temperature for 4 h then concentrated in vacuo to dryness. The residue was diluted with ethyl acetate (100.0 mL). X 100, 0 ml), washed, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness EtOAc EtOAc EtOAc EtOAc Oxy)-2-phenyl]-1-[(5-carbyl, phene-2-yl)methyl]-1,3-dihydro-2-indole-2-one (2.90 g, 61%), as a colorless solid: mp 173: 175. (: ; iHNMR (300MHz, CDC13) 5 9.11 (s, 1H), 7.3-7.27 (m, 5H), 7.18 (dd, J = 7.5, 7.5 Hz, 1H) , 7.09 (d, J = 3.8 Hz , 1H), 7.06 (dd, J = 7.9 Hz, 1H), 6.97-6.86 (m, 3H), 6.79-6.68 (m, 3H), 5.04 (ABq, 2H), 4.91 (s, 2H), 4.84 ( s, 1H) ; 13C NMR (75 MHz, CDCI3) δ 175.9, 151.5, 149.7, 142.8, 138.8, 137.8, 130.2, 128.8, 128.2, 128.1, 128.1, 128.0, 127.4, 126.8, 125.2, 124.2, 122.7, 117.6, 117.6, 116.3, 143924-sp-20091127-1 -243- 201020257 114.9, 109.1, 70.2, 48.1, 38.6; MS (ES+) m/z 464.3 (Μ + 1), 462.3 (Μ + 1). C· 3· [5·(竿oxy)_2_hydroxyphenyl]_ι_[(5. fluorenyl thiophene-2-yl)methyl]3·(methyl)-1,3-dihydro-2Η-吲嗓Synthesis of 2-ketone at 〇 °C '3-[5-(yloxy)-2-hydroxyphenylindole-[(5-alkylρ-sept-2-yl)indenyl]-1 , 3-dihydro-2Η-indol-2-one (2.80 g, 6.07 mmol), polyoxymethylene (0 73 g '24·3 mmol) in tetrahydropyran (1 〇.〇 ml To the mixture was added an aqueous solution of sodium hydroxide (0.97 g, 24.3 mmol) in water (1 mL). The reaction solution was stirred for 2 hours, and then the reaction was quenched by adding 1% aqueous hydrochloric acid (30.0 mL). The reaction mixture was extracted with ethyl acetate (3 χ 5 mL). The combined organic solution was washed with EtOAc (EtOAc m. The filtrate was concentrated in vacuo to dryness. The residue was triturated with diethyl ether, EtOAc (EtOAc) Mercapto)-1,3-dihydro-2-indole-2-one (2.71 g, 91%) as colorless solid: MS (ES+) m/z 494.2 (M+l), 492.3 ( Μ + 1 ). Preparation 39 3-[4-(decyloxy)-2-hydroxyphenyl]_ι_(diphenylmethylhydrazine, dihydro-2H啕哚·2-one® Synthetic Α·3·[4·(爷Synthesis of oxy)-2-hydroxyphenyl]small (diphenylmethyl)_3·hydroxy·^ dihydro·2h(tetra) 嗓_2_嗣 at 〇°C, in 3-(benzyloxy)-prepared (8.7 g , 435 mmol; in a stirred solution of tetrahydrofuran (1 mL), slowly add isopropyl hydrazine magnesium oxide (227 mL, 2M tetrahydrofuran solution, 45·4 mmol). It is stirred under 30 knives # and in the vacuum to shrink to dry. Add two gas to burn (9). 143924-SP-20091127-1 -244- 201020257 ml), then, at 〇 ° C, add ι_ (diphenyl hydrazine A solution of 411_吲哚_2,3_dione (12.4 g, 39.5 mmol) in dioxane (5 mL). The mixture was stirred at room temperature for 16 hours and quenched with saturated aqueous ammonium sulfate. The organic layer was washed with water, dried over sodium sulfate, and filtered. The solution was concentrated to dryness in vacuo. The obtained solid was recrystallized from ethyl acetate / hexane to give 3-[4-(hydroxy)-2-hydroxyphenyl]-1-(diphenylmethyl)-3-hydroxy-1,3 -Dihydro-2H-indol-2-one (19.60 g, 97%) as colorless solid: 1H NMR (300 MHz, CDC13) δ 7.49-7.43 (m, 1H), 7.42-7.25 (m, 13H) , 7.23-7.17 (m, Ο 2H), 7.12-7.04 (m, 2H), 6.91 (s, 1H), 6.72-6.62 (m, 2H), 6.51-6.44 (m, 1H), 6.39 (dd' J = 8.6, 2.4 Hz, 1H), 4.99 (s, 2H); MS (ES+) ra/z 536.3 (M + 23). B. Synthesis of 3-[4-(hydroxy)-2-phenyl]pyrene(diphenylmethyl)4}dihydro-2Η·ρ5丨哚·2·one 3-[4-(Benzyl) Oxy)-2-phenyl]-1-(diphenylindenyl)-3-trans-yl-1,3-dihydro-2-indole-2-one (10.0 g ' 19.5 mmol), three A mixture of ethyl decane (15.6 ml, 97.5 mmol) and trifluoroacetic acid (15.0 mL, 195 mmol) was mixed and stirred at 0 °C for 20 min. The mixture was concentrated under vacuum. The residue was triturated with diethyl ether to give 3-[4-((oxy)-2-hydroxyphenyl]-1-(diphenylmethyl)-1,3-dihydro-2?-indole-2 - ketone (7.40 g '76%) as colorless solid: NMR (300 MHz, CDCI3) δ 7.44-7.25 (m, 14H), 7.23-7.17 (m, 2H), 7.11-7.02 (m, 2H), 6.95 (s, 1H), 6.81 (d, J = 8.6 Hz, 1H), 6.68 (d, J = 2.5 Hz, 1H), 6.55-6.49 (m, 1H), 6.46 (dd, J = 8.6, 2.6 Hz , 1H), 5.09 (s, 1H), 4.99 (s, 2H); MS (ES+) m/z 498.3 (M + 1). Preparation of 40-hydroxy-4-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b.]difuran-3,3·-吲143924 -sp-20091127-1 -245* 201020257 嗓Η, (2Ή)-yl) fluorenyl] benzoate quinone imine amide synthesis in 4-[(2'-keto_5,6-dihydrospiro[ Benzene like seven: 5,4-btfuran-3,3,-吲嗓]-1'(2Ή)-yl)methyl]benzonitrile (1.3 g, 329 mmol) in the second A solution of the amine in water (% by volume) was added to the stirred solution in (10 ml). The reaction was heated' and stirred at 8 ° C for 1 hour then cooled to ambient temperature and the product was precipitated by the addition of distilled water (25 mL). The solid was filtered and dried to give N,_hydroxy.4_[(2,-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b1]difuran-3, 3,-啕哚]-Γ(2Ή)-yl)methyl] benzoquinone imine amide (1.32 g '93%) as a colorless solid: iHNMR (300MHz, CDCl3) ❹ δ 9.17 (s, 1H) , 7.40-7.03 (m, 13H), 6.99-6.92 (m, 2H), 6.79-6.74 (m, 2H), 6.58-6.50 (m, 1H), 5.10 (s, 1H) ; MS (ES+) m/ z 428.0 (M + 1). Preparation 41 2-(4'·Gas-2'-oxaspiro[furobenzobenzodioxene-7,3,_ 哚Η 哚Η, (2Ή)-yl)-N,-[(cyclopropyl) Synthesis of carbonylcarbonyl)oxy]acetamidoamine amides 2-(4·-carbyl-2'-oxo[Miso-[2,3^^3]benzodioxolene-7 ,3,_ 吲哚]-Γ(2Ή)-yl)-Ν'-hydroxyethyl hydrazide amide 1.4 g, J 〇 millimoles, diisopropylamine (0.16 g, 1.6 mmol) And a stirred solution of cyclopropane gasified carbon hydrazine (〇 16 g, © 1.6 mmol) in dichloromethane (20 mL) was stirred at ambient temperature for 16 h. The colorless solid which precipitated from the solution was filtered, washed with water (5 ml) and diethyl ether (5 ml) to give 2-(4,-chloro-2-, oxaspiro[furo[2,3-f][ 1,3]benzodioxanthene _7,3,_啕哚Η,(2Ή)_* ) N,_[(cyclopropylcarbonyl)oxy]acetamimine amide, a colorless solid (〇25g, 53%): i H nmr (300 MHz, DMSO-de) δ 7.31 (dd, J = 8.0, 8.0 Hz, 1H), 7.02 (d, J = 8.0 Hz, 2H), 6.64 (br s, 2H), 6.54 (s, 1H), 6.47 (s, 1H), 5.88 (s, 2H), 4.77 (ABq, 2H), 143924-sp-20091127-l _ 246 (S) 201020257 4.43 (ABq, 2H), 1.75-1.67 (m, 1H), 0.86-0.73 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) δ 176.9, 171.9, 156.5, 153.6, 148.9, 144.8, 141.9, 130.8, 130.0 , 128.6, 117.4, 108.8, 104.4, 101.8, 104.5, 101.8, 104.4, 101.8, 93.0, 77.5, 58.4, 11.7, 8.45, 8.42; MS (ES+)m/z 456.1 (M+ 1), 478.1 (M +23) 〇Preparation of 42 Ν'-hydroxy-2-(2i-oxabuffo[2,3-f][l,3]benzodioxolene-7,3'_吲哚]-1' Synthesis of (2Ή)-yl) acetamimidamine in 2'-oxo[furo[2,3-f][l,3]benzodioxene-7,3,_吲]_ © 1 '(2Ή)-yl)acetonitrile (2.00 g, 6.25 mmol) in a mixture of ethanol (40 ml) and diterpene (5 ml), hydroxylamine (25·0 g, 1.6) Milliliter, 50% by weight solution in water). The reaction solution was stirred at ambient temperature for 2 hours to form a colorless precipitate. Filter the solids. The residue was washed with water (3×20 mL) and dried to give 1ST-hydroxy-2-(2'- oxo[2,3-f][l,3] benzodiox Igneene-7,3'-吲哚]-Γ(2Ή)-yl)acetamidamine (1.88 g, 85%) ' is a colorless solid: mp 235-238 ° C; iHNMR (300 MHz, DMSO -d6) _ J 9.20 (s, 1H), 7.26 (dd, J = 7.7, 7.7 Hz, 1H), 7.10 (d, J = 7.3 Hz, 1H), 6.99 ❹ (dd, J = 8.6, 8.6 Hz, 2H), 6.65 (s, 1H), 6.28 (s, 1H), 5.89 (d, J = 1.8 Hz, 2H), 5.49 (s, 2H), 4.70 (ABq, 2H), 4.29 (s, 2H); 13 C NMR (75 MHz, DMSO-d6) δ 177.1, 155.7, 148.7, 147.9, 143.0, 142.1, 132.3, 129.1, 123.7, 123.3, 120.5, 110.0, 103.9, 101.8, 93.6, 80.2, 57.8, 40.3 ; ES+) m/z 354.18 (M + 1), 337.2 (M - 17). Preparation 43 3-[(2'-_ Group-5,6-dihydrospiro[benzo[i,2-b: 5,4h']di-p-pentan-3,3,-吲嗓]-Γ Synthesis of (2Ή)-yl)methyl]benzoquinone 143924-sp-20091127-1 -247- 201020257 on 5,6-dihydrospiro [stupid [i,2-b: 5,4-b,] Difuran-3,3,-anthracene-2,(1Ή)-one (0.97 g, 3.46 mmol) in 2-butanone (25 ml), cesium carbonate (3.39 g, 10.39) Millol) with α-bromo-m-benzoquinone (0.85 g, 4.33 mmol). The mixture was heated to reflux over 2 hours, cooled to ambient temperature and filtered. The solid was washed with ethyl acetate. The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate-hexane (1:5-1:1) and then recrystallized from ethyl acetate and diethyl ether to give 3[[2] ,__基_5,6_ Dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3,-吲哚]-1,(2Ή)-yl)methyl Benzoonitrile (1_26 g '92%) as a colorless solid: mp 187. H; iHNMR (300 © MHz, CDC13) δ 7.61-7.58 (m, 3H), 7.47-7.44 (m, 1H), 7.25-7.19 (m, 2H), 7.07-7.03 (m, 1H), 6.73-6.71 (m, 1H), 6.43-6.41 (m, 2H), 5.11-4.70 (m, 4H), 4.53 (d, J = 9.0 Hz, 2H), 3.09-2.91 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 178.1, 162.0, 161.4, 141.5, 137.5, 132.6, 131.9, 131.6, 130.7, 129.9, 128.9, 124.3, 123.9, 120.2, 119.9, 118.7, 118.4, 113.1, 108.8, 93.4, 80.5, 72.5, 57.7 , 43.4, 29.0 ; MS (ES+) m/z 394.8 (M + 1). Preparation of 44 Ν'-hydroxy-3-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-啕) Synthesis of ❹ 嗓Η '(2Ή)-yl)methyl]benzene oxime imine decylamine in 3-[(2-keto-5,6-monohydrospiro[benzo[l,2-b: 5] , 4-b'] two bite α South _3,3'-4丨ρ flower]_ 1 (2 Η)-yl)methyl]benzonitrile (1.15 g, 2.92 mmol) in dimethyl hydrazine The solution in (2 〇 ml) was added with amine (50% by weight in η 2 ,, 2 mL, 32.67 mmol). The reaction was stirred at 80 ° C for 3 hours and cooled to ambient temperature. By filtering 'collecting the temple, washing the knee with water and acetazone, and drying in vacuum' to obtain N·-carbyl-3-[(2'-keto-5,6-dihydrospiro[benzene And [i,2_b : 5,4-b,] 143924-sp-20091127-1 -248- (8) 201020257 difuran-3X哚]-Γ(2Ή)-yl) decyl] benzoquinone imine amide ( 〇85g, 68%) : 1H NMR (300 MHz, CDC13) δ 7.61 (m, 1H), 7.96 (m, 1H), 7.51 (m, 1H), 7.38 (m, 2H), 7.16 (m, 2H) ), 7.01 (m, 1H), 6.75 (m, 1H), 6.48 (s, 1H), 6.40 (s, 1H), 5.09 (d, 1H, J = 15.7 Hz), 4.98 (d, 1H, J = 9.0 Hz), 4.83 (m, 3H), 4.70 (d, 1H, J = 9.0 Hz), 4.49 (t, 2H, J = 8.6 Hz), 2.96 (m, 2H) ; MS (ES+) m/z 427.8 (M + 1). Preparation of 45 6-{[ s(1-indolyl)toluene]oxy} snail [i_benzofuran_3,3,_吲® 哚]-2'(1Ή)-one 6-Hydroxyspiro[1-benzofuran-3,3'-indole]-2,(1Ή)-one (3.0 g, 11.8 mmol) in anhydrous hydrazine, hydrazine-dimercaptocarboxamide In a solution of 30 ml), add imidazole (1.97 g '28.9 mmol) and gasified triisopropyl decane (6 〇 3 mL, 28.5 mmol) under nitrogen. The reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated in vacuo to dryness. The residue was extracted twice with ethyl acetate (50 mL). &lt;&quot;&quot;&quot;&&&&&&&&&&&&&&&&&& Ethyl ester, 6-{[ s(1-methylethyl) decyl]oxy μ benzobenzopyran-3,3'-吲嗓]-2'(1Ή)-one (2.68 g, 69) % yield) as colorless solid: 1H NMR (300 MHz, CDC13) δ 8.48-8.08 (br, 1H), 7.29-6.90 (m, 4H), 6.10 (d, J = 8.1 Hz, 1H), 6.50 ( d, J = 2.1 Hz, 1H), 635 (dd, J = 8.1, 2.1 Hz, 1H), 4.96 (d, J = 9.0 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 1.34- Preparation of 46 l'-[(2R)-tetrahydrofuran-2-ylindenyl]-6-{[((indolylethyl)-indolyl]oxy} snail [1,8 (m, 21H) ° -Synthesis of benzofuran-3,3'-indole]-2'(1Ή)-one 143924-sp-20091127-1 -249- 201020257 at 6-{[((methylethyl)) Alkyl]oxy} spiro[μbenzofuran_3,3,·4 哚]-2'(1Ή)-one (2.46 g, 6.0 mmol) in anhydrous hydrazine, Ν-dimercaptoamine In a solution (10 ml), add sodium hydride (0.24 g, 6.0 mmol) at 0 ° C under nitrogen. . The mixture was stirred at (TC for 2 min, then (4-)-(4-hydrofuranyl)methyl 4-methylbenzenesulfonate (1.69 g, 6.6 mmol). The reaction mixture was stirred at ambient temperature 30 After a few minutes, then heat to 6 ° C for 5 hours. The reaction was quenched with saturated aqueous ammonium chloride (1 mL) and poured into water (15 mL). The combined organic solution was washed with water (2×50 ml) and brine (50 ml), dried over sodium sulfate sulfate, filtered and concentrated. 25% ethyl acetate, which gives 1'_[(2 feet)_tetrahydro p-sodium 嗔_2_yl fluorenyl]-6-{[shen (1-mercaptoethyl) oxalate] oxygen }[[[p. , 1Η), 7.14-6.98 (m, 3H), 6.53 (d, J = 8.1 Hz, 1H), 6.48 (d, J = 2.1 Hz, 1H), 6.32 (dd, J = 8.1, 2.1 Hz, 1H) , 4.95-4.90 (m, 1H), 4.66 (d, J = 9.3

Hz, 1H), 4.34-4.22 (m, 1H), 4.00-3.66 (m, 4H), 2.10-1.66 (m, 4H), 1.34-0.98 (m, 21H) ; MS (ES+) m/z 494.2 ( M + 1) 〇© Preparation 47 5,6-One snail [1-Benzo oxime-3,3^51嗓]-2'(1Ή)-ketone synthesis Α· 3-(4,5-difluoro Synthesis of 2-hydroxyphenyl)-1 benzoquinone)_3 via hydrazino 2Η_嘀哚_2_嗣 in 3,4-difluorophenol (10.33 g, 79.4 mmol) in anhydrous tetrahydrofuran (6 Inside the solution in 〇ml), in 〇. Isopropylmagnesium chloride (39 7 ml, 79.4 mmol) was added under nitrogen and the solution was stirred at ambient temperature for 3 hours. -250- 143924-sp-20091127-1 (S) 201020257 Tetrahydrofuran was removed by rotary evaporation and the residue was redissolved in anhydrous dihydrate (140 ml). The solution was cooled to nitrogen, then N-diphenylmethylhydrazine (13.77 g &apos; 43.9 mmol) was added and the mixture was allowed to warm to ambient. After 3 days, the reaction was quenched with saturated aqueous EtOAc (EtOAc) and concentrated in vacuo. The residue was redissolved in ethyl acetate (1% EtOAc) and washed with water (2 &lt;RTI ID=0.0&gt;&gt; The residue is precipitated from diethyl ether to give 3-(4,5-difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)-3-carbyl 4,3-dihydro-2H-W ❹ Indole-2-one (12.08 g, 61%) as a colorless solid: 1H NMR (300 MHz, CDC13) 5 9.23 (br s, 1H), 7.47-7.44 (m, 1H), 7.35-7.21 (m, 9H ), 7.18-7.11 (m, 2H), 6.90 (s, 1H), 6.83 (dd, J = 11.2, 6.9 Hz, 1H), 6.67 (dd, J = 11.2, 8.7 Hz, 1H), 6.56-6.51 ( m, 1H), 4.13 (br s, 1H); MS (ES+) m/z 426.2 (M -17). Synthesis of B·3-(4,5-difluoro-2-hydroxyphenyl)-l-(diphenylmethyl)·l,3-dihydro-2H-indol-2-one from 3-(4) ,5-Difluoro-2-hydroxyphenyl)-1-(diphenylindenyl)-3-hydroxy-1,3-dihydro-2H-W 0 嗓-2-嗣 (II·72 g, 26.4 m Mohr) solution in trifluoroacetic acid (60 ml)

Triethyl decane (10.55 ml, 66.0 mmol) was added under nitrogen, and the mixture was stirred 16 hr. After concentration in vacuo, the residue was purified eluting with EtOAc EtOAc EtOAc Precipitation from diethyl ether / hexanes followed by filtration to give 3-(4,5-difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)-1,3_dihydro-2H-W 哚-2- Ketone (6.29 g, 56%) as colorless solid: 4 NMR (300 MHz, CDC13) δ 9.27 (br s, 1H), 7.37-7.12 (m, 12H), 6.94 (s, 1H), 6.87 (dd, J = 11.3, 7.1 Hz, 1H), 6.76 (dd, J = 11.2, 8.9 Hz, 1H), 6.58-6.56 (m, 1H), 5.12 (s, 1H) ; MS (ES+) m/z 428.2 (M + 1). 143924-sp-20091127-l -251- 201020257 C· 1 -(monophenylmethyl)·5,6-monofluorospiro[1·benzopyrene·3,3′_fruit】_2,(rH) The synthesis of the ketone in 3-(4,5-difluoro-2-hydroxyphenyl)-1 n-phenylmethylhydrogen-2H吲哚_2-one (6.30 g, 14.7 mmol) in anhydrous tetrahydrofuran (12 In a solution of 〇ml), a carbonic acid planer (14.4 g '44.2 mmol) was added under argon, followed by the addition of thiol iodide (3.21 mL, 44.2 mmol). After 20 hours, the reaction mixture was concentrated in vacuo and purified eluting with ethyl acetate (5 <RTIgt; The aqueous layer was extracted with ethyl acetate (6×50 mL). Several products were filtered off as a colorless precipitate. The combined organic solution was washed with EtOAc (EtOAc m. Precipitate from diethyl ether/hexane to obtain Γ-(diphenylfluorenyl)_5,6-difluorospiro[ι_benzopyrene _3,3,_ 4 嗓]-2'(1Ή)-one (4.51 g , 70%), as a colorless solid: m.p. </ s </ s </ s </ s </ s>; H NMR (300 MHz, CDC13) δ 7.41-7.26 (m, 10H), 7.15-7.12 (m, 1H), 7.08-6.97 (m, 3H), 6.78 (dd, J = 10.5, 6.3 Hz, 1H), 6.54 (d, J = 8.4 Hz, 1H), 6.44 (dd, J = 9.0, 7.8 Hz, 1H), 5.03 (d, J = 9.0 Hz, 1H ), 4.77 (d, J = 9.3 Hz, 1H) , 1 3C NMR (75 MHz, CDC13) δ 176.8, 156.6 (d, J = ll.〇Hz), 151.2 (dd, JC-f = 248.2, 14.5 Hz ), 145.6 (dd, JC.F= 241.5, 13.85 Hz), 141.7, 137.4, ® 137.1, 131.5, 128.8, 128.8, 128.7, 128.3, 128.3, 128.1, 128.0, 124.2 (dd, J = 6.4, 3.3 Hz) , 123.8, 123.3, 112.4, 111.5 (dd, J = 20.4, 1.6 Hz), 100.1 (d, J = 22.4), 80.8, 58.9, 57.5 ; MS (ES+) m/z 440.2 (M + 1), 462.2 ( M + 23). D. Synthesis of 5,6-difluorospiro[1-benzofuran_3,3'_吲哚]-2·(1·Η)-嗣 from 1'-(diphenylmethyl)-5,6- Difluorospiro[1-benzofuran-3,3'-indole]-2,(1Ή)-one (6.06 g ' 13.8 mmol) in decyl alcohol (1 mL), ethyl acetate (25 In a solution of ML) and acetic acid (1 ml), under argon, in a steel-shaped container, 143924-SP-20091127-1 -252- (8) 201020257 Add le (20%, on activated carbon Upper 5〇% h2 〇, 2.0g, 3.76 Home Mo). Place the bullet-shaped container under hydrogen (5 psi) and at 65. (The mixture was heated for 16 hours. The reaction mixture was filtered over EtOAc EtOAc EtOAc (EtOAc)EtOAc. ,6-difluorospiro[μbenzofuran_3,3,_^丨哚]_2ι(1Ή)-one (3,63 g '96%), as colorless solid: melting point &gt; 2 〇 (rc ; 1 η NMR (3〇〇ΜΗζ, CDC13) &lt;5 8.00 (s, 1H), 7.32-7.27 (m, 1H), 7.15-7.05 (m, 2H), 6.97 (d, J = 7 8 Hz. 1H) , 6.79 (dd, J = 10.3, 6.3 Hz, 1H), 6.62 (dd, J = 9.0, 8.0 Hz, 1H), 5.00 (d, J = 9.2 Hz, 1H), 4.73 (d, J = 9.2 Hz, 1H) ; 13C NMR (75 MHz, CDC13) 6 179.7, 156.70 (d, J = 10.9), 151.3 (dd,jc f= 248 7, 14 3 Hz), 145.7 (dd, Jc-F= 241.6, 13.8 Hz ), 140.3, 131.6, 129.4, 124.0, 123.7, 123.4 (dd, J = 6.3, 3.1 Hz), 111.9 (d, J = 20.4 Hz), 110.7, l〇〇.l (d, J = 22.4 Hz), 80.7, 58.4; MS (ES+) m/z 274.2 (M + 1). Preparation 48 Ν '--yl-3-(2'-fluorenyl-6H-spiro[benzofuran[6,5_卿, 3] Synthesis of dioxolene hydrazine _7,3-dihydroanthracene H'-yl) acrylamide amide 3-(2-keto-6H-spiro[benzopyrano[6,5-d][l,3]dioxosylylene-7,3,_dihydroanthracene]-fluorenyl) Add a hydroxylamine (5 〇 wt% solution in water, 16 mL, 24 mmol) in a stirred solution of propionitrile (2.00 g '6.0 mmol) in diterpenoid (15 mM). The reaction was stirred at ambient temperature for 16 hours, then the product was allowed to settle upon addition of water/ethanol (3:1, 1 mL). The solvent was decanted and the residual solid was taken in distilled water (75 mL) The solid was filtered and air-dried to obtain Ν'-carbyl-3-(2'-keto-6H-spiro[benzopyranodioxanthene-7,3·.dihydroindole]. · 基 基 醯 , , 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 143 Preparation 49 4-Alkyl-3-hydroxy-3-(6-hydroxy-1,3-benzodioxanthene-5_ylindole, 3-dihydro-2-indole-indot-2-one Synthesis in a solution of 1,3-benzodioxol-5-ol (4.86 g, 22.0 mmol) in anhydrous tetrahydrofuran (1 mL) at 〇 °C Propyl gasification town / gluten solution (49.6 mmol, 24.8 ml, 2. 〇m solution in tetrahydropyrene), after 10 minutes. The reaction mixture was stirred for 3 minutes, at this time, A portion of 4-chloroguanidine (4.00 g, 22.0 mmol) was added. The reaction mixture was stirred at ambient temperature for 2 hours and quenched by the addition of 1% aqueous hydrochloric acid (25.0 mL). The mixture was concentrated to dryness in vacuo. The residue was purified eluting with ethyl acetate (1 mL) Filtration. The filtrate was concentrated to dryness in vacuo. The residue was crystallised from hot diethyl ether to afford 4-[3-hydroxy-1,3-benzodioxolene _5_ Base)-1,3-dihydro-2H-choline-2-one (6.70 g) '95%), as a beige solid: m.p. 25〇-253°C; 1 H NMR (300 MHz, DMSO-d6) δ 10.30, (s, 1H), 9.04 (s, 1H), 7.20 (s, 1H) ), 7.12 (t, J = 8.0 ^

Hz, 1H), 6.74 (d, J = 8.2 Hz, 1H), 6.70 (d, J = 7.7 Hz, 1H), 6.45 (s, 1H), 6.17 (s, 1H), 5.88 (d, J = 6.7 Hz, 2H); 13 C NMR (75 MHz, DMSO-d6) &lt;5 178.1, 148.6, 147.0, 145.6, 139.6, 130.6, 130.1, 129.6, 122.3, 118.6, 108.9, 108.4, 101.1, 97.4, 75.8; MS (ES-) m/z 304.2 (M - 17), 302.2 (M -17). Preparation of 50 4-Alkyl-3-(6-carbyl-1,3-benzodioxol-5-yl)-1,3-dihydro-2H-p5indol-2-one 143924-sp-20091127-1 -254- (S) 201020257 At ambient temperature, each of the gas radicals (6-carbyl-U-benzodioxanthene-5-yl)-1 , 3-dihydron (tetra) 2 ketone (6 gram, 18 8 mM) in a solution of anhydrous chloroform (7 〇. 〇 ml), adding three said acetic acid (30.7 g, 269 mM) ) with Triethyl Dream House (then milliliters, 131 grams, 113 millimoles). The reaction mixture was scrambled for 2 hours at ambient temperature. The reaction was quenched with water (0.5 ml) and the solid was filtered. The solid was triturated with diethyl ether to give 4·chloro-3-(6-light-yl-i,3-benzodioxanthene _5-based (4) dioxane 2 Η·(5)-noise _2 ketone (4·71)克, 83%), as colorless solid: m.p. 210-225t: (decomposition); MS (ES+) ❿ -3G4.1 (Μ + 1), 3G2.1 (Μ + 1). Preparation 51 4-Chloro- 3-(6-Hydroxy-U-benzodioxol-2-ylindole, 3 bis(hydroxymethyl η, 3_一风-2Η-ρ5|嗓-2-嗣 synthesized in 4-chloro-3 -(6-hydroxy-l,3-benzodioxanthene-5_yl η,3_dihydro 2 Η 吲哚-2-one (4.5 g, 14.9 mmol), polyoxymethylene (1.78 g) , 59. 4 mmol) In a suspension of water (50.0 ml), add an aqueous solution of sodium hydroxide (2 38 g, 59 4 mmol) in water (10 ml). The mixture was stirred at 0&lt;0&gt;C for 2 h and quenched with 10% EtOAc (EtOAc &lt;RTI ID=0.0&gt;萃取. 〇ml) extraction. The combined organic solution was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated to dryness in vacuo. The scale was developed to give 4-oxyl-3-(6-hydroxy-1,3-benzodioxanthene-5_ylindole, 3-bis(fluorenyl)-1,3-dihydro-2Η - anthracene-2-one (3.91 g, 72%) as a colorless solid: mp. &lt;&quot;&quot;&quot;&quot;&quot;&quot;&quot;&gt; , 6.99 (d, J = 7.7 Hz, 1H), 6.86 (s, 1H), 6.83 (d, J = 8.2

143924-sp-20091127-1 -255- 201020257

Hz, 1H), 6.18 (s, 1H), 5.87 (d, J = 11.0 Hz, 2H), 5.03 (q, J = 10.8 Hz, 2H), 4.86 (br, 1H), 4.64 (ABq, 2H); 13C NMR (75 MHz, DMSO-d6) &lt;5 177.9, 150.3, 146.9, 146.8, 139.9, 129.1, 129.0, 128.6, 122.7, 116.0, 108.8, 107.6, 101.2, 97.7, 63.6, 63.3, 56.6; MS (ES+ m/z 364.2 (M + 1), 346.2 (M -17). Preparation 52 4'-Gas-based snail [Miso-[2,3-f][l,3]benzodioxene _7,3,-诩哚]_2, (1'H)- _ Synthesis at 4-°C in 4-alco-3-(6-hydroxy-1,3-benzodioxosin-5-yl)-1,3-bis(indenyl)-1, Add 3-tribute phosphine (2.53 g, 12.5 mmol) to a solution of 3- hydrazine-2H-M </RTI> </RTI> ketone (3.63 g, 10.0 mmol) in anhydrous tetrahydrofuran (100.0 mL) This was followed by a solution of di-tert-butyl azodicarboxylate (2.88 g, 12.5 mmol) in dry tetrahydrofuran (25.0 mL). The reaction solution was stirred at 0 ° C for 1 hour, followed by addition of ammonium hydroxide (1 mL). The reaction mixture was stirred for an additional 2 hours. The reaction was quenched with 1% aqueous hydrochloric acid (100.0 mL). The reaction solution was extracted with ethyl acetate (3×1 mL). The combined organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to dryness in vacuo. The residue was purified by flash chromatography using ethyl acetate in hexane to give 4,-chloro-spiro[[,,,,,,,,,,,,,,,, -7,3'-Chao 哚]-2'(1Ή)-one (0.98 g, 31%), as colorless solid: mp 175-185. (: ; 1H NMR (300 MHz, DMSO-d6) 5 10.81 (s, 1 Η), 7.24 (t, J = 8.0 Hz, 1H), 6.94 (d, J = 8.2 Hz, 1H), 6.86 (d, J = 7.1 Hz, 1H), 6.59 (s, 1H), 6.28 (s, 1H), 5.90 (d, J = 2.5 Hz, 2H), 4.74 (ABq, J = 9.5 Hz, 2H) ; 13 C NMR (75 MHz, DMSO-d6) δ 178.4, 157.0, 148.8, 144.2, 141.9, 130.9, 130.3, 129.2, 123.0, 117.5, 109.4, 103.3, 101.9, 93.3, 77.8, 58.9; MS (ES+) 143924-sp-20091127-1 -256- 201020257 m/z 318.3 (Μ + 1), 316.3 (Μ + 1) 〇 Preparation 53 2-(4'-Gasyl-21-oxo snail [吱 并 迎 迎 迎 苯 苯 二 氧 圜 圜 圜_7 3, (5) 嗓Η '(2Ή)-yl)-Ν'-hydroxyethyl hydrazide amide synthesis at ambient temperature in 4,-chloro-2,-oxo snail [吱 并 [2 , 3-f][l,3]benzodioxanthene-7,3,-,哚Η(2Ή)-yl)acetonitrile (1.81 g, 5·10 mmol) in ethanol (25.0 ml) Hydroxylamine (0.67 g '20.4 ml) was added to the solution in dimethyl hydrazine (3 mM). The yellow reaction solution was stirred for 2 hours at which time a yellow precipitate formed. The precipitate was filtered, washed with water (100.0 mL) and dried under vacuo to give 2-(4,-carbyl-2,-oxaspiro[2,3-fl[l,3]benzene And dioxolene _7,3'-吲哚]-1·(2Ή)-yl)-N--hydroxyacetammine amide (1.54 g '78%)' is a fluffy yellow solid: melting point I8〇_185«»c ; ihnmr(3〇〇MHz, DMSO-d6) δ 9.20 (s, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.01 (d, J = 3.8

Hz, 1H), 6.98 (d, J = 3.5 Hz, 1H), 6.60 (s, 1H), 6.32 (s, 1H), 5.60 (d, J = 3.8 Hz, 2H), 5.54 (br, 2H), 4.78 (ABq, J = 9.6 Hz, 2H), 3.68 (s, 2H); 13 C NMR (75 MHz, DMSO-dg) δ 176.8, 156.6, 148.9, 147.7, 145.1, 141.9, 130.8, 129.9, 128.5, 123.5, 117.5, 109.1, 103.7, 101.9, 93.2, 77.5, 58.4, 40.9; MS (ES+) m/z 388.1 (M + 1). Preparation 54 1·-[(2-keto-1,3-tetrahydrocarbazol-5-yl)indolyl]spiro[唉,[2,3-f][l,3]benzodiox Synthesis of alkene-7,3'-anthracene-2'(1'11)-ketone will be snail [吱,[2,3-,3]benzodioxolene-7,3, _啕哚]-2,(1Ή)-ketone (1.37 g '4.99 mmol), 5-(methylmethyl)-1,3-tetrahydrocarbazol-2-one (1.34 g, 5.38 mmol) Ear) and carbonated planer (2.39 g, 7.34 mmol) in a mixture of hydrazine, hydrazine-dimethyl 143924-sp-20091127-1 -257- 201020257 carbamide (8.0 ml), mixed at ambient temperature η hours, and filtered. The solid was washed with ethyl acetate and the filtrate was washed with water (3 <RTIgt; The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography to give keto-1,3-tetrahydroxazol-5-yl)indolyl] snail [bito-[2,3-f][l,3] benzo Dioxolene-7,3,-啕哚]-2'(1Ή)-one (0.56 g '25%): melting point 195-202 ° C; WNMROOOMHz, CDC13) δ 7.35-7.30 (m, 1H) , 7.17-7.04 (m, 3H), 6.50 (s, 1H), 6.12 (s, 1H), 5.84 (s, 2H), 5.27 (br, 1H), 5.02-4.96 (m, 1H), 4.91-4.87 (m, 1H), 4.68-4.64 (m, 1H), 4.14-3.96 (m, 2H), 3.75-3.68 (m, 1H), 3.55-3.44 (m, 1H); 13 C NMR © (75 MHz, CDCI3) δ 178.9, 158.5, 155.9, 149.0, 142.4, 142.2, 131.7, 129.4, 124.0, 123.9, 119.2, 109.6, 102.8, 101.6, 93.7, 80.3, 74.9, 58.1, 43.5, 43.1; MS (ES+) m/z 403.2 (M + 23), 381.2 (M + 1). Preparation 55 3-(6-Pyryl-1,3-benzodioxanthene _5_yl)_3_(thiol)_7_(trifluoromethyl-azonium-2-net synthesis A· 3- mercapto-3-(6·carbyl·1,3-benzodioxol-5·yl)_7•(trifluoromethyl)_ 1,3·dihydro-2ΕΜ丨哚-2 - Synthesis of ketones @ at 0 C, in a solution of 1,3-benzodioxanthene _5_ leaven (9.63 g, 69 7 mmol) in anhydrous tetrahydrofuran (200 ml) Add isopropylmagnesium sulphate solution (92.9 mmol, 46.5 ml, 2. 〇μ solution in tetrahydrofuran) over 30 minutes. Add 7-trifluoromethyl hydrazine in one portion (4 gram) , 22.0 mmol. The reaction mixture was stirred at ambient temperature for 4 h and then quenched with EtOAc EtOAc EtOAc EtOAc Ethyl acetate (2 〇〇 ml) diluted 143924-sp-20091127-1 - 258 - 201020257 release 'washed with saturated ammonium chloride (3 x 30.0 ml), brine (3 x 30.0 ml), dehydrated with anhydrous sodium sulfate Dry and filter. Concentrate the filtrate to dryness in vacuo The residue was triturated with hot diethyl ether to give 3-hydroxy_3_(6-hydroxyl-benzo-oxo-oxo-5-yl)-7-(trifluoromethyl)-i,3-dihydro -2H-indol-2-one (13.6 g '83%): iHNMRpOOMHz.DMSO-dd 5 10.65 (s, 1H), 9.21 (s, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.22 (s, 1H), 7.07 (d, J = 7.2 Hz, 1H), 6.95 (dd, J = 7.7, 7.7 Hz, 1H), 6.57 (s, 1H), 6.17 (s, 1H), 5.89 (d, J = 6.2 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) ¢5 179.2, 148.6, 147.3, 141.0, 139.9, 135.7, ® 127.9, 125.3, 124.3, 121.7, 119.8, 110.1, 107.2, 101.2, 97.7 , 73.9 ; MS (ES-) m/z 352.2 (M -1). Β· 3-(6-carbyl·1,3·benzodioxol.5-yl)_7_(trifluoromethyl +3. Synthesis of dihydro-2H·indol-2-one at ambient temperature in 3-hydroxy-3-(6-hydroxy-1,3-benzodioxol-5-yl) -7-(Trifluoromethyl)-1,3-dihydro-2H-indol-2-one (7.06 g, 20.0 mmol) in anhydrous difluoroacetic acid (21.0 mL ' 9.12 g, 80 mmol) In the solution, φ was added with triethylsulfonate (12. 8 ml, 9.30 g, 80.0 mmol). The reaction mixture was stirred at ambient temperature for 0.5 hours. The reaction mixture was quenched with water (5 mL). The mixture was extracted with ethyl acetate (2 mL 150 mL). The organic solution was washed with saturated aqueous ammonium chloride (3×75 ml), dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. The residue was triturated with diethyl ether to give 3-(6-hydroxy-1,3-benzodioxol-2-yl)-7-(trifluoromethyl)-1,3-dihydro-2-indole- Indole-2-one (5.94 g, 88%) ' is a colorless solid: iHNMR (300MHz, DMSO-d6) (5 10.81 (s, 1H), 9.25 (br, 1H), 7.37 (d, J = 8.0 Hz , 1H), 7.12 (d, J = 7.3 Hz, 1H), 6.98 (dd, J = 7.7, 7.7 Hz, 1H), 6.71 (s, 1H), 5.88 (s, 2H), 4.65 143924-sp-20091127 -1 -259- 201020257 (s,1H),13c NMR (75 MHz,DMSO-d6) &lt;5 178.7, 150.5, 147.4, 140.5, 140.1,133.3, 127.8, 124.3, 124.2, 121.6, 115.5, 110.8, 110.3 , 101.3, 98.2, 48.1; MS(ES+)m/z338.3 (M + l) 〇C. 3-(6-methyl-1,3-benzodioxanthene.5-yl) each ( Synthesis of methyl)-7-(trifluoromethyl)-1,3-dihydro-2Η-吲哚-2·one by 3-(6-hydroxy-1,3-benzodioxanthene) 5_yl)_7_(trifluoromethyl)yisodihydro-2-indole-2-one (5.64 g ' 16.7 mmol), polyoxymethylene (! 78 g, 59.4 mmol) in tetrahydrofuran (20.0 ml) Add sodium hydroxide (2.68 g, 66.9 mmol) to the suspension in water (5 〇.〇 ml) Aqueous solution of water in water (3 〇. 〇 ml). The reaction mixture was stirred at 〇 ° C for 1 hour and quenched with 1% hydrochloric acid (50.0 mL). The combined organic solution was washed with saturated ammonium sulfate (3×5 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. Purification by chromatography to give 3_(6-hydroxy-indole, 3_benzodioxol-5-yl)-3-(hydroxymethyl)_7•(trifluoromethylhadihydro-2H_蜊哚_2_ ketone (4.56 g, 73%) ' is a fluffy solid: 1 η NMR (300 MHz, DMSO-d6) δ 10.63 (s, 1 Η), 9.16 (s, 1H), 7.32 (d, J = 7.9 Hz, 1H), 7.08 (d, J = 7.2 Hz, ^ 1H), 7.01 (s, 1H), 6.94 (dd, J = 7.7, 7.7 Hz, 1H), 6.18 (s, 1H), 5.88 (s, 2H), 5.03 (br, 1H), 3.97 (ABq, J = 9.9 Hz, 2H); 1 3 C NMR (75 MHz, DMSO-d6) δ 180.5, 150.3, 146.8, 141.5, 140.0, 136.0, 127.5, 123.8 , 121.0, 117.7, 109.7, 108.4, 101.2, 97.9, 60.2, 55.2; MS (ES+) m/z 390.2 (M + 1). Preparation of 56 7X trifluoromethyl) snail [pyrano[2,3-f][l,3]benzodioxanthene-7,3,-啕哚]-2'(ΓΗ)-one Synthesis 143924-sp-20091127-1 26〇(S) 201020257 At 0 ° C, in 3-(6- via a 1 q# private, H-1,3-benzodioxene _5_ group )_3_(曱曱7-(trifluoromethyl)-1,3-dihydro-2H 11 # ο //I _»· Oxygen 2Η-吲木-2-one (4.10 g, η.7 毫Add a solution of butyl ketone (10) ml, 283 g, 13.9 mmoles, followed by di-tert-butyl azodicarboxylate (3.22 g, in a solution of vinegar k M M 100.0 ml). 13.9 millimoles) solution in ethyl acetate (ml). The reaction solution was stirred at 0 C for 30 minutes, followed by the addition of 1% hydrochloric acid (5 liters of p) of the reaction solution to 10% hydrochloric acid (2 x 50.0 ml), saturated ammonium sulfate (3 χ 5 〇 ml) and brine (3 X Washing with 50 ml), the organic solution was dried over anhydrous sodium sulfate, and β was passed over. The mash was concentrated to dryness in vacuo. The residue was purified by flash chromatography to give 7? Alkyl snail [biting benzodioxanthene-7,3'-W 嗓]-2'(1Ή)-one (3.59 g '88%): melting point 245-248. (: ; 4 NMR ( 300 MHz, DMSO-d6) δ 11.02 (s, 1Η), 7.50 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 7.3 Hz, 1H), 7.11 (dd, J = 7.5, 7.5 Hz, 1H), 6.66 (s, 1H), 6.32 (s, 1H), 5.90 (d, J = 3.1 Hz, 2H), 4.74 (ABq, 2H) ; 13 C NMR (75 MHz, DMSO-d6) δ 179.4, 156.0, 148.9, 139.7, 134.9, 128.3, 125.8, 125.7 (m), 122.9, 119.7, 112.0, 111.4 (m), 103.6, 101.9, 93.7, 80.4, 57.5; MS (ES+) m/z 350.3 (M + 1 57 Preparation 57 3-[2-(2|-oxabendazole) [2,3-£][1,3]benzodioxosylene-7,3'-吲哚]-Γ (2Ή)-yl)ethyl]hexahydropyridine-1-decanoic acid tert-butyl ester The synthesis is at ambient temperature, in the snail [gorge[2,3-f][l,3]benzodioxanthene _7,3ι_ 哚 哚]-2'(1Ή)-ketone (0.96 g) , 3.41 mmol; in a mixture of 2-butanone (17 ml) and acetone (Π ml), add carbonic acid planer (3.79 g, 11.6 mmol) and N-Boc-3-(2-bromo group) Ethyl) hexahydropyridinium (1.00 g, 3.42 mmol). The mixture was stirred at ambient temperature for 16 hours. The reaction mixture was filtered and taken to propyl 143924-sp-20091127-1 •261 · 201020257 ketone (2 x 50 ml) Wash. Concentrate the filtrate to dryness in vacuo. Purify the residue by column chromatography eluting with ethyl acetate (10% to 30% gradient) '-Oxygen snail [吱,[2,3-Hungry 1,3] benzodioxene-7,3'-p bud]-1'(2Ή)-yl)ethyl]hexahydro p 唆-1--1-carboxylic acid tert-butyl ester (1.48 g, 88%) as a white powder: m.p. 64-67 ° C (diethyl ether /hexane); 1H NMR (300 MHz, CDC13) δ 7.30 (dt , J = 7.8, 0.9 Hz, 1H), 7.16 (d, J = 7.3 Hz, 1H), 7.50 (dt, J = 7.5, 0.7 Hz, 1H), 6.92 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.10 (d, J = 1.7 Hz, 1H), 5.86 (dd, J = 6.0, 1.0 Hz, 2H), 4.90 (dd, J = 9.0, 0.6 Hz, 1H), 4.65 (dd, J = 9.0, 3.0 Hz, 1H), 3.90-3.69 (m, 4H), 2.97-2.86 (m, 1H), 2.77-2.68 (m, ® 1H), 1.96-1.92 (m, 1H), 1.76-1.16 (m, 15H) ; 13C NMR (75 MHz, CDC13 ) 177.2, 155.8, 154.8, 148.8, 1423, 142.2, 142.1, 132.4 (2), 128.9, 124.0, 123.2, 119.4 (2), 108.5, 102.9, 101.4, 93.6, 80.4, 79.4, 58.1, 38.2, 33.5, 30.7, 30.7, 30.6, 30.5, 28.4, 24.3 ; MS (ES+) m/z 515.4 (M + 23). Preparation 58 3-[2-(2'-oxaspiro[furo[2,3-f][l,3]benzodioxolene-7,3,_吲哚]_ 1'(2Ή) Synthesis of -ethyl)ethyl]hexahydroindole β at 〇 ° C in 3-[2-(2'-oxaspiro[吱,[2,3-f][l,3]benzodiox伍 烯 丨哚 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 -1 羧酸 羧酸 羧酸 羧酸 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ In the solution, add trimethylacetic acid (4 ml). The mixture was stirred at ambient temperature for 2 hours and concentrated to dryness in vacuo. The residue was diluted with dioxane (1 mL), washed with saturated aqueous sodium bicarbonate (2×30 mL), water (3 mL) and dried over anhydrous sodium sulfate. And concentrated in a vacuum to dry wine to obtain 3-[2-(2'-oxo[[,3,3-f][l,3] benzodioxolanene-7,3, ... 143924-sp-20091127-1 -262· 201020257 哚]-1'(2Ή)-yl)ethyl]hexahydrop specific bite (0.72 g '60%): MS (ES+) m/z 393.4 (Μ + 1). Preparation 59 5-[(2'-oxaspiro[furo[2,3-f][l,3]benzodioxene-7 7哚]_Γ(2Ή)_yl)methyl]-2 Synthesis of -(trifluoromethyl)indol-3-hypoacidic acid ethyl ester in snail [吱,[2,3-f][l,3] stupid and dioxoquinone]_2'(ΓΗ) -_ (4.26 g '15.10 mmol) in a solution of 2-butanone (120 ml), adding carbonic acid planer (14.76 g, 45.30 mmol) and 5-(bromodecyl)-2-( Trifluoromethyl) 咬 Bite ° South Winter Sour Ethyl Acetate (Lyalin, VV et al, Zhumai Organic Heskoi Khimii (1984), 20 (4): 846) (4.80 g, 15.90 mmol). The reaction mixture was heated to 70 ° C at 6 ° C, cooled to ambient temperature over 18 hours, and filtered. The solid was washed with ethyl acetate. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography using ethyl acetate and hexane to give 5-[(2. ,3-f][l,3]benzodioxanthene-7,3'-啕哚]-Γ(2Ή)-yl)indolyl]-2-(trifluoromethyl)furan-3- Ethyl carboxylate (4.65 g, 61%): mp 162-164. 〇 ; 1H NMR (300 MHz, CDC13) δ 7.23-7.17 (m, 2Η), 7.12-7.06 (m, 1H), 6.94 (d, J = 7.8

Hz, 1H), 6.76 (s, 1H), 6.50 (s, 1H), 5.86-5.85 (m, 2H), 5.05-4.87 (m, 3H), 4.68-4.64 (m, 1H), 4.31 (q, J = 7.2 Hz, 2H), 1.32 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDC13) δ \112, 160.4, 155.9, 150.6, 149.1, 143.5, 142.5, 141.1, 132.0, 129.1, 124.2, 124.0, 120.7, 120.0, 119.0, 116.4, 111.1, 108.7, 103.0, 101.6, 93.7, 80.4, 61.7, 58.2, 36.7, 13.9; MS (ES+) m/z 502.1 (M + 1). Preparation 60 5-((2'-keto-6H-spiro[benzofuro[6,5-d][l,3]dioxosyl-7,3·-dihydro 143924-sp-20091127 -1 -263· 201020257 啕哚Η,-yl)methyl)_2_(trifluoromethyl)furan carboxylic acid synthesized in 5-[(2,-oxo snail [吱鸣和[2,3船3] Benzodioxolone _7,3,_巧丨1] (2H)-yl)methyl]_2_(difluoroindolyl)-trim_3_carboxylic acid ethyl ester (13 gram, 2 whit To a solution of ethanol (8 ml) and water (1.7 ml), sodium hydroxide (0.12 g, 3.00 mmol) was added. The reaction mixture was heated under reflux for 45 minutes and concentrated in vacuo to remove ethanol. To the residue, water (15 ml) was added and the mixture was acidified to pH~3 with 1% hydrochloric acid. The resulting mixture was extracted with ethyl acetate (3 x 5 mL). The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo to give 5-((2'-keto-6H-spiro[benzofuro[6,5-d][l,3]dioxos-ene-7,3,- Dihydrogen, H,-yl)methyl)_2-(trifluoromethyl)furancarboxylic acid (1.03 g '84%): mp 195-197. (: ; WNMRpOOMHz 'DMSO-A) δ 7.13-7.26 (m, 1H), 7.17-7.15 (m, 2H), 7.05-7.00 (m, 2H), 6.67 (s, 1H), 6.09 (s, 1H) , 5.90-5.88 (m, 2H), 5.11-4.96 (m, 2H), 4.80-4.66 (m, 2H); 13C NMR (75 MHz, DMSO-d6) 5 177.0, 161.9, 155.8, 152.3, 148.9, 142.2 , 141.9, 141.5, 132.1, 129.3, 124.1, 123.8, 122.2, 120.6, 120.1, 117.0, 111.8, 109.7, 103.1, 101.9, 93.8, 80.1, 57.9, 36.7; MS (ES-) m/z 472.0 (M - 1 ). Xin Preparation 61

Γ-(4-bromoindenyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran_3,3'_W 哚]-2'(ΓΗ The synthesis of the ketone makes 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3W丨哚]-2,(1Ή)-one (1.12 g) , 4.0 mM), 4-bromo bromide (1.00 g, 4.0 mmol) and carbonated (6.50 g, 20.0 mmol) in methyl ethyl ketone (20 mL). Under reflux for 3 hours. Cooling the reaction mixture to ambient temperature, 143924-sp-20091127-1 -264- 201020257

And filter,. The solid was washed with propyl I (50 ml). The filtrate was concentrated to dryness in vacuo. The residue was purified by column chromatography using 20% to 80% gradients of ethyl acetate in hexanes to give s-(4-bromo-decyl)-5,6-dihydrospiro[benzo [l,2-b: 5,4-b']difuran-3,3,-anthracene-2,(1Ή)-one (1.60 g, 89%) as colorless solid: 1H NMR (300 MHz , DMSO-d6) 5 7.49-6.98 (m,7Η), 6.75 (d,J

=7.7 Hz, 1H), 6.43 (s, 1H), 6.42 (s, 1H), 4.89 (ABq, 2H), 4.82 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H), 3.08-2.90 (m, 2H) ; 13 C NMR (75 MHz, DMSO-d6) δ in.9, 161.9, 161.3, 141.8, 134.8, 132.7, 132.0, 129.2, 128.7, 124.0, 123.6, ® 121.7, 120.0, 120.0, 118.8 , 109.0, 93.3, 80.6, 72.4, 57.7, 43.6, 29.0; MS (ES+) m/z 448.1 (M + 1), 450.1 (M + 1) 62 Preparation 62 2-[(2'-keto-5, 6-Dihydrospiro[benzo[l,2-b: 5,4-b,]dioxan-3,3,-呻嗓]-Γ(2Ή)-yl)methyl H,3-carbazole Synthesis of methyl 4-carboxylate such that 5,6-dihydrospiro[benzo[i,2-b:5,4-b']di-n-but-3,3'-吲嗓]-2' ( 1Ή)-ketone (1.00 g '3.3 mmol), 2-(gas methyl)$azole-4-methyl-acid methyl ester (2.00 g, η.4 mmol) and carbonic acid planer (4.00 g, 12.3 The mixture was suspended in methyl ethyl ketone (50 ml) and refluxed under nitrogen for 5 hr. The reaction mixture was allowed to cool to ambient temperature & filtered. The solid was washed with acetone (5 mL). The filtrate was concentrated to dryness in vacuo. The residue was purified by column chromatography using a gradient of 30% to 70% of ethyl acetate in hexane to give 2-[(2'-keto-5,6-dihydrospiro[benzo[ i,2-b : 5,4-b']difuran_3,3,-,哚]-1,(2Ή)-yl)methyl]-1,3-11 Ester (0.88 g, 61%) as colorless solid: 1 u NMR (300 MHz, DMSO-dg) δ 8.17 (s, 1H), 7.27-6.91 (m, 4H), 6.53 (s, 1H), 6.38 ( s, 1H), 5.12 (ABq, 2H), 4.81 (ABq, 2H), 4.51 (t, J = 8.7 Hz, 2H), 3.89 (s, 3H), 143924-sp-20091127-l 201020257 3.04-2.91 ( m,2H) ; 13 C NMR (75 MHz, DMSO-d6) 5 177.6, 161.9, 161.2, 161.2, 159.2, 145.0, 141.0, 133.6, 132.5, 129.0, 124.1, 120.1, 119.9, 199.1, 108.8, 93.2, 80.5 , 72·4, 57.7, 52.3, 37.2, 29.0; MS (ES+) m/z 419.2 (M + 1). Preparation 63 2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3'-吲哚]-Γ( 2Ή)-yl)methyl]-1,3-saki. The synthesis of sit-4-reaction acid will be 2-[(2^-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3·-吲哚]-1'(2Ή)-yl)mercapto]-1,3-1,3-oxazole-4-carboxylic acid methyl ester (0.88 g, 2.1 mmol) with sodium hydroxide (4.00 g, 10.0 mmol) The suspension mixture in water (50 ml) and methanol (50 ml) was stirred at 60 ° C for 2 hours. The reaction mixture was concentrated in vacuo to remove most of the methanol and acidified to pH 1-2 with concentrated hydrochloric acid. The solid residue was filtered off and washed with water (50 ml) and dried in vacuo to give 2-[(2'-keto-5,6-dihydrospiro[benzo[1,2-b:5] ,4-b,]difuran-3,3,-accord]-Γ(2Ή)-yl)methyl]-1,3-oxazole-4-carboxylic acid (0.64 g, 75%), colorless Solid: 1H NMR (300 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.29-6.95 (m, 4H), 6.55 (s, 1H), 6.37 (s, 1H), 5.08 (ABq, 2H), 4.74 (ABq, 2H), 4.44 (t, J = 8.7 Hz, 2H), 3.01-2.80 (m, 2H); MS (ES-) m/z 403.4 (M -1). Preparation 64 2-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxol-7,3'4丨哚]-1'(2Ή)- Synthesis of methyl]-1,3-ρ#0 sitting-4-rebel vinegar snail [furo[2,3-f][l,3]benzodioxolene-731-吲哚]-2'(1Ή)-ketone (1.60 g, 5.70 mmol), 2-(methyl-methylmethoxazole-4-carboxylic acid methyl ester (1.00 g, 5.70 mmol) and carbonic acid planer (3.71 g, 11.4 mmol), the suspension mixture was refluxed for 16 h in tetrahydrofuran (10 mL). The mixture was cooled to 143924-sp-20091127-1 -266-201020257 ambient temperature and concentrated in vacuo. The residue was taken up in EtOAc (EtOAc (EtOAc)EtOAc. Purification by column chromatography, using a gradient of 20% to 30% of ethyl acetate in hexane to give 2-[(2'- oxo[[,,,,,,,,,,,, Benzodioxanthene _7,3,-啕哚]-1·(2Ή)-yl)methyl]-1,3-oxazole-4-carboxylic acid methyl ester (2.19 g, 92%) , as a colorless solid: melting point 1 83-185°C; eNMRGOOMHz'DMSO-i^) 5 8.86(s, 1H), 7.28 (t, J = 7.2 Hz, 1H), 7.16 (d, J = 7.0 Hz, 1H), 7.09 (d, J = 7 8 Hz V 1H), 7.03 (t, J = 7.5 Hz, 1H), 6.66 (s, 1H), 6.41 (s, 1H), 5.90 (d, J = 2.1 Hz, 2H), 5.23-5.17 ( m, 2H), 4.74 (ABq, 2H), 3.74 (s, 3H); 13 C NMR (75 MHz, DMSO-d6) (5 177.2, 161.3, 160.2, 155.6, 148.8, 146.9, 142.3, 142.0, 132.8, 132.4, 129.4, 124.1, 123.9, 120.4, 109.7, 103.9, 101.9, 93.7, 80.0, 57.9, 52.3, 37.4; MS (ES+) m/z 421,2 (M + 1). Preparation 65 2-[(Τ- Oxy snail [吱-benzo benzodioxene _7,31_old 哚] Γ(2Ή)_ ^ yl)methyl]-1,3-oxazole-4-carboxylic acid synthesized in 2-[ (2'-oxo snail [cough and 0^,3] benzodioxolane _7,3,,吲哚]_ 1'(2Ή)-yl)methyl]-1,3 azole _4-Carboxylic acid methyl ester (1.17 g, 2.79 mmol) in tetrahydrofuran (20 mL), add sodium hydroxide (45 g, lu millimoles) in water (5 liters) Solution. The mixture was stirred for a while under reflux. After cooling to ambient temperature, the mixture was acidified with concentrated hydrochloric acid (2 mL). The reaction mixture was concentrated in vacuo to remove aq. EtOAc (EtOAc) The combined organic solution was dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo to dryness. Residues 143924-SP-20091127-1 •267 - 201020257 Residues were prepared with diethyl ether and ethyl acetate to give 2-[(2'-oxaspiro[furo[2,3-f][1,3]benzene And dioxynene-7,3'-rhodium]-1'(2)-yl)methyl]-1,3-oxazole-4-hypoacid (0.65 g, 58%), colorless Solid: 1H NMR (300 MHz, DMSO-d6) δ 13.07 (br, 1 Η), 8.74 (s, 1H), 7.29 (t, J = 7.7 Hz, 1H), 7.17 (d, J = 6.6 Hz, 1H) , 7.10 (d, J = 7.8 Hz, 1H), 7.04 (t, J = 7.5 Hz, 1H), 6.66 (s, 1H), 6.34 (s, 1H), 6.04 (s, 2H), 5.20-5.08 ( m, 2H), 4.73 (ABq, 2H); 13 C NMR (75 MHz, DMSO-d6) 5 177.1, 162.2, 159.9, 155.7, 148.8, 146.4, 142.2, 142.1, 133.8, 132.2, 129.4, 124.1, 123.9, 120.3, 109.7, 103.8, 101.9, 93.7, 80.0, 57.8, 31.2; MS (ES+) m/z 407.1 (M + 1) ° Preparation 66 4'-Bromo-l'-((5-(trifluorodecyl) ), succinyl-2-yl) fluorenyl)-5,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3'-dihydroanthracene-2-- Synthesis of ketones in 4'-&gt; odoryl-5,6-dihydro-2H-spiro[benzopyrene-β-nan[6,5-b]吱-3,3,-dihydro-p-丨哚]-2'-ketone (0.64 g '1.8 mmol) in 2-butanone (25 ml) Adding carbonic acid planer (1.75 g '5.3 mmol) in a stirred solution followed by 2-(bromomethyl)-5-(difluoromethyl)pfan (0.51 g, 2.2 mmol) ). The mixture was refluxed for 16 hours&apos; cooled to ambient temperature, filtered, and concentrated in vacuo to dryness. The residue was subjected to column chromatography (hexane / ethyl acetate, from 3:1 to 1:1) to give 4'-bromo-indole-((5-(trifluoromethyl)pf- 2-yl)mercapto)-5,6-dihydro-2H-spiro[benzofuro[6,5-b]furan-3,3,-dihydroanthracene-2,-one (0.82 g) , 90%), as colorless solid: mp 165-167 ° C; 4 NMR (300 MHz, CDC13) &lt;5 7.27-7.10 (m, 2H), 6.92 (td, J = 6.9, 1.8 Hz, 1H), 6.77-6.70 (m, 1H), 6.44-6.33 (m, 3H), 5.15-4.96 (m, 2H), 4.91-4.76 (m, 2H), 4.53 (dt, J = 8.6, 1.9 Hz, 2H), 2.98 (t, J = 8.5 Hz, 2H); 13C NMR (75 MHz, CDC13) 5 177.3, 162.4, 162.2, 151.6, 143924-sp-2009H27-l -268- 201020257 143.4, 141.8 (q, J = 43.0 Hz ), 130.2, 127.7, 120.0, 119.7, 118.8 (q, J = 267.1 Hz), 118.4, 117.0, 112.6, 109.5, 107.7, 92.9, 77.1, 72.4, 59.0, 37.0, 28.9 ; MS (ES+) m/z 505.8 (M + 1), 507.8 (M + 1). Preparation 67 6-Fluoro-5-methoxyspiro[l- benzofuran_3,3,_吲哚]_2, (1Ή), the synthesis of Α· 1-(diphenylmethyl)·3·( Synthesis of 4-fluoro-2-hydroxy-5-anthraceneoxyphenyl)-3-yl-l-1,3-dihydroindole-2-pyrene in 3-fluoro-4-methoxyphenol (Niemann, Μ. B. / Am. Oiern. to. (1941), _ 63 : 609) (4.60 g, 32.4 mmol) in a solution in tetrahydrofuran (60 ml), add isopropyl gasification at 5 C. A solution of tetrahydro-p-depleted (18.0 mL '36.0 mmol). The tetrahydrogen bitum was removed under reduced pressure and dioxane (60 mL) was added. In this solution, a solution of 1-(diphenylmethylHH-indole-2,3-dione (8.00 g, 25.5 mmol) in dichloromethane (6 mL) was added and The reaction mixture was stirred for 16 hours at ambient temperature. The reaction mixture was quenched with saturated aqueous ammonium sulfate (5 mL). The mixture was reacted and dried over magnesium sulfate, filtered, and evaporated under reduced pressure. Column chromatography, using a gradient of 4% to 9〇% of ethyl acetate in hexane, knowing 1-(diphenylmethyl)_3_(4-fluoro-2-yl-5-indole Oxyphenyl)_3_trans-yl-1,3-dihydro-2H-indol-2-one (6.60 g, 57%) as a pink solid: Ms (ES+) m/z &gt;438.3 (M-17 B. Synthesis of 1-(diphenylindenyl)-3-(4-fluoro-2-hydroxy-5-methoxyphenyl)4,3.dihydro-2Η-ρ5丨ρ多-2-明At 0 C, in 1-(diphenylindenyl)-3-(4-fluoro-2-ylpyridyloxyphenyl)-yl-1,3-monohydro-2-indole-2-one ( 6.60 g, 14.5 mmol) in a solution of diethylene bromide 143924-sp-20091127-1 201020257 (100 ml), adding triethylamine (455 g, 45 〇 millimolar) with sulfur dichloride醯( 3.57 g, 30.0 mmol). The reaction mixture was heated under reflux for 1 h. The reaction mixture was cooled to ambient temperature and concentrated under reduced pressure to dissolve the residue in tetrahydrofuran (1 mL). Acetic acid (1 ml) and zinc powder (6 54 g, 1 〇〇. 〇 mmol) were added in small portions at ambient temperature. The reaction mixture was stirred at ambient temperature for 16 hours and filtered. The filtrate was concentrated to dryness in vacuo. EtOAc m. 2-yl-2-yl-5-methoxyphenyl)_1,3-dihydro-2H-p?indol-2-one (1.1 〇β 克 '17%) ' is a colorless solid: ms (ES+) ra /z 440.2 (Μ + 1). C. 1'·(Diphenylmethyl)·6•Fluoro-_s_methoxyoxyindole benzofuran-3,3,·(5)哚]_ 2'(1Ή )--Synthesis of a ketone will be 1-(monoethyl)-3-(4-fluoro-2-hydroxy-5-anthraceneoxyphenyl)-indole, 3-dihydro-2Η-indol-2-one (1.10 g, 2.5 mmol), gas-based iodonane (〇7 g, 4 mmol) and barium carbonate (2.60 g, 8.0 m) The suspension was stirred at ambient temperature for 24 hours in tetrahydromethane (5 mL). The reaction mixture was filtered. The solid was washed with acetone (5 mL). The filtrate was concentrated in vacuo to dry. Purify the residue by column chromatography using a gradient of 20% to 70% of ethyl acetate in hexanes to give y-(diphenylmethyl) 6 fluoro-5 methoxy benzopyran -3,3'·吲哚]_2, (1,H)-one (0.49 g, 43%), m. D. 6-Fluoro-5-methoxyspiro[ι_benzofuran.3,3,_,哚]·2, (1Ή) the synthesis of Γ-(diphenylfluorenyl)_6-fluoro group 5_Methoxysulfonium benzofuran_3,3,_啕嗓]-2'(1Ή)-嗣 (0.49 g, 1.09 mmol), triethyldecane (〇23 g, 2.0-270-) The suspension mixture of 143924-sp-20091127-1 (S) 201020257 millimolar) and trifluoroacetic acid (0.57 g, 5.0 mmol) was refluxed under nitrogen for 5 hours. The reaction mixture was allowed to cool to ambient temperature and concentrated under reduced pressure. The oily residue was sonicated with hexane (10 mL) for 10 min, and the solid product was filtered to give &lt;RTIgt;6-fluoro-5- </RTI> <RTIgt; ?丨哚]-2'(1Ή)-ketone (0·29 g, 92%) as a colorless solid: 4 NMR (300 MHz, DMSO-d6) δ 9.28 (s, 1 Η), 7.37-6.91 (m, 4H), 6.74 (d, J = 11.0 Hz, 1H), 6.39 (d, J = 8.3 Hz, 1H), 4.82 (ABq, 2H), 3.68 (s, 3H) ; 13 C NMR (75 MHz, DMSO- D6) (5 180.0, 155.2, 154.9, 154.7, 151.9, 142.9, 142.7, 140.2, 132.1, ® 129.2, 124.1, 123.6, 122.7, 122.7, 110.4, 109.0, 108.9, 100.0, 99.7, 80.5, 58.8, 57.2; (ES+) m/z 285.8 (M + 1). Preparation 68 1-(Diphenylmethyl)-7-fluoro-3-(7-hydroxy-2,3-dihydro-1,4-benzodi Synthesis of oxodecene _6-yl)-1,3-dihydroanthracene-2-one A. Synthesis of 7-fluoroyl-1·(diphenylmethyldodeto-2,3-dione) The procedure described in Preparation 26, and irrelevant changes were carried out, and 2,3-dihydro-6Η-[1,4]dioxene terpene was replaced with 7·fluoroyl hydrazine [2,3 -fHl 哚-7,8-dione' and replacing 2_(bromomethyl)5 (trifluoromethyl) with bromodiphenyl decane to obtain 7-fluoro 4-(diphenylmethyl) -1Η-ρ5丨嗓-2,3-dione (80%): MS (ES+) m/z 353.7 (M + 23) B. 1-(diphenylfluorenyl).7·fluoroyl_3 _hydroxy_3_(7. hydroxyl -2,3_Dihydro·^benzodioxanthene-6-yl)-1,3-dihydro-2Η·(4)哚·2_one is synthesized in 2,3-dihydro-indole, 4 Addition of isopropyl gasification town to a cooled (〇.〇) suspension of benzodipine ruthenium (yield 47 g, 3 〇 mmol) in anhydrous tetrahydrofuran (12 ml) 2Μ solution in tetrahydrofuran 'L7 ml, 3 3 mmol 143924-SP-20091127-1 •271- 201020257 ear). The reaction mixture was stirred at (TC) for 1 hour, and 7-fluoro small (diphenylmethyl HH) was added. -+多-2,3-二_ (1. gram, 3 〇 millimoles) with anhydrous di-methane (1 mL). The reaction mixture was stirred at ambient temperature for 19 hours. Concentrate in vacuo and dilute with saturated aqueous solution (3 mL) and ethyl acetate (30 mL). The liquid phase was separated and the aqueous phase was extracted with ethyl acetate (2 χ 5 mL). The combined organic extracts were washed with brine (1 mL) dried over anhydrous sodium sulfate. The crude product was purified by column chromatography and eluted with ethyl acetate in hexanes from 8% to 66% of hexanes to give 1-(diphenylmethyl)-7-fluoro-hydroxyl_3 (7-hydroxyl) _2,3 dihydrochun-1,4-benzodioxanthene _6_yl) dihydrogen 2 Η吲哚 2 ketone 22 g, 8 enough, as an off-white solid: MS (ES+) m/ Z475.0 (M-17). C. 1-(Diphenylmethyl)_7-fluoro-3-(7.hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3· Synthesis of dihydro-2Η矧哚-2·one from 1-(diphenylmethyl)-7-fluoro-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzene And dioxordecene-6-yl)-1,3-dihydro-2-indole-2-one (4.27 g, 8.8 mmol) in di-acetic acid (100 mL) in (Triethyl decane (2.8 ml '18 mmol) was added under TC, and the reaction mixture was concentrated in vacuo. EtOAc was purified eluting Dissolve to 66% of the gradient solution, and obtain μ(diphenylmethyl) 7-fluoro group (7-hydroxy-2,3 dioxo-1,4-benzodioxanthene-6-yl)-1, 3-Dihydro-2H-indol-2-one (2.5 g, 61%), as a colorless solid: MS (ES+) m/z 465 9 (M+1). Preparation 69 4'-(&gt;Smelly B醯基)·Γ_Methyl_2 3_2 argon snails smoldering [2,3_ secret, 4] benzodioxene terpene-8,3,-(4)哚]-2, (1Ή) - Synthesis of ketones 143924-sp-20091127-l

-272- 201020257 4- 4-indenyl-1'-mercapto-2,3-dihydrospiro[p-benzobenzodioxene-8,3W丨哚]-2,(1Ή)-_ (0.15 g, 0.41 mmol) in a solution of anhydrous tetrahydrofuran (5 ml), phenyltrimethylammonium tribromide (〇 16 g, 0.41 mmol), and the reaction mixture at ambient temperature Stir for 丄 hours. Water (30 ml) was added, and after stirring for 5 minutes, the mixture was partitioned between brine (3 ml) and ethyl acetate (30 ml). The aqueous phase was extracted with ethyl acetate (2×20 mL), and the combined organic extracts were washed with brine (2 mL), dried over anhydrous sodium sulfate, filtered, and evaporated in vacuo. Yellow oil. This oil was dissolved in di- methane (4 mL) and diethyl ether (30 mL) was added to precipitate. The solid was collected by vacuum filtration, washed with diethyl ether (10 ml), dried, and dried under high vacuum to give 4 (m. [2,3-g][i,4]benzodioxanthene-8,3'-吲嗓]-2'(1Ή)-鲷 (0.125 g, 70%), as an off-white solid: ihnmr ( 300 MHz, CDC13) δ 7.51-7.42 (m, 2H), 7.13-7.08 (m, 1H), 6.49 (s, 1H), 6.02 (s, 1H), 4.93-4.78 (m, 2H), 4.22-4.02 (m, 6H), 3.28 (s, 3H); MS (ES+) m/z 429.4 (M + l), 431.4 (M + 1) 70 Preparation 70 3-(Γ-indolyl-21-keto-1 ',2,2',3-tetrahydrospiro[p-f-[2,3-g][l,4]benzodioxanthene-8,3'-蚓哚]-4'-yl The synthesis of ethyl 3-ketopropionate in a suspension of sodium hydride (60% w/w dispersion in mineral oil, 0.11 g, 2.8 mmol) in anhydrous tetrahydrofuran (10 ml) Diethyl carbonate (0.26 mL, 2.1 mmol) was added at ambient temperature and the mixture was heated at reflux for 5 min. Add 41-acetyl-fluorenyl-mercapto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3' -吲哚]-2·(1Ή)-ketone (0.50 g, 1.4 U3924-sp-200911274-273-201020257 millimolar)' and the reaction mixture was heated under reflux for 16 hours, allowed to cool to ambient temperature and Pour into water (75 ml). The mixture was extracted with dichloromethane (3 χ 5 mL). The combined organic extracts were washed with brine (5 mL) dried over anhydrous sodium sulfate. Purify the crude product by column chromatography and dissolve it in a gradient of 醋酸% to 1% by weight of ethyl acetate in dichloromethane, followed by recrystallization from a gas-burning/acetonitrile to give 3 (丨, Methyl-2-mercapto-1,2'2',3-tetrahydrospiro[吱,[2,3-g][i,4]benzodioxanthene_8,3'_ 吲Ethyl]-4'-yl)-3-ketopropanoic acid ethyl ester (0.235 g, 39%) as pale yellow solid: H NMR (300 MHz, CDC13) δ 7.50-7.43 (m, 2 Η), 7.14- 7.09 (m, 1H), 6.51 ® (s, 1H), 6.02 (s, 1H), 4.97-4.78 (m, 2H), 4.20-4.03 (m, 6H), 3.89 (d, J = 15.6 Hz, 1H ), 3.65 (d, J = 15.6 Hz, 1H), 3.29 (s, 3H), 1.16 (t, J = 7.1 Hz, 3H); MS (ES+) m/z 445.8 (M + 23). Preparation 71 3-(2,2-Fluoro-6-yl-l-1,3-benzodioxol-5-yl) small {[5-(trifluoromethyl)furan-2-yl]anthracene Synthesis of aryl}-1,3-dihydro-2H-indol-2-one A. 3_(2,2-difluoro-6-hydroxy-1,3·benzodioxolene-5. )_3_hydroxy·heart sand (trifluoromethylpyran-2-yl)indolyl, 3. synthesis of dihydro-2-indol-2-one® in 2,2-—gas-1,3- Addition of isopropyl gasification town (in tetrahydrogen p) at 0C in a solution of Benzooxol (Jacobus et al., WO 2004/ 4048320) (1.15 g, 6.60 mmol) in anhydrous tetrahydrofuran The solution in Fusing, 3.3 ml, 6.6 mmol.) The reaction mixture was stirred at rc for 5 hours, and 1-{[5-(di-mercapto)-pyran-2-yl] fluorenyl group was added. Bow noise _2,3-di_ (1.95 g, 6.60 mmol). The reaction mixture was allowed to warm to ambient temperature and stirred for 1 hour. Add saturated aqueous solution (30 ml) and acetic acid The mixture was extracted with an ester (3 χ 3〇 143924-sp-20091127-l - 274 - (8) 201020257 ml). The combined organic extracts were washed with brine (2 x 3 ml) and dried over anhydrous sodium sulfate. Filtration, and concentration in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate in hexane to 5% to 35% gradient to give 3-(2 2 -difluoro_6_hydroxy^- Benzodioxol-5-yl)-3-carbyl-1-{[5-(trifluoromethyl)pyran-2-yl]methyl}13 dihydro-2H吲嗓-2- _ (2·54 g '73%) ' is a light orange solid: MS (ES+) 451.3 (M _ 17). Β· 3·(2,2-difluoro-6-radio-i,3-benzene And dioxolene _5-based) 丨 丨 三氟 三氟 三氟 三氟 失 失 失 失 -2- -2- -2- -2- -2- -2- -2- -2- -2- -2- -2- 合成 · · · · · · · · _2 _2 合成 合成 合成 合成 合成 合成 合成2'2-difluoro-6-hydroxy-1,3-benzodioxanthene _5-yl)3 hydroxy small {[5·(difluoromethyl)pyran-2-yl]methyl b 13 _Dihydro·2Η啕哚_2 ketone (2.5 g, 5 32 mmol) in a solution of anhydrous monooxane (1 mL) in diethyl decane (4.2 mL, 〇{&gt;c) The mixture was warmed to ambient temperature and stirred for 72 h and concentrated in vacuo. In hexane

Preparation 72

\中所,十处的程序' and the implementation of irrelevant changes, 143924-sp-20091127-1 Dihydro-2-indole ketone synthesis -275. 201020257 using 1-(methoxy fluorenyl)_1H_吲哚_2,3_dione (Tr〇st and Frededksen, A sigh (10) C/iem. Μlike to batch 2005, 44(2): 308-310) to replace 1-{[5-(trifluoromethyl) gnach -2-yl]hydrazinib 1Η-嘀哚-2,3-dione, 3_(2,2-difluoro-6-hydroxy-1,3-benzodioxanthene-5-yl) 3-Hydroxy 4-(decyloxymethyl)-1,3-dihydro-2Η-indol-2-one (48%) 'Yellow-brown amorphous solid: 4 NMR (300 MHz, CDC13) &lt;5 9.20 (br s, 1H), 7.50-7.40 (m, 2H), 7.29-7.21 (m, 1H), 7.13 (d, J = 7.7 Hz, 1H), 6.77 (s, 1H), 6.53 ( s, 1H), 4.45 (br s, 1H), 5.15-5.04 (m, 2H), 3.30 (s, 3H). B. 3-(2,2-Difluoro-6-hydroxy-1,3-benzodioxol.5-yl)·ι·methyl-]L,3_dihydrogen·2Η·4 The synthesis of indole-2-one was carried out according to the procedure described in Preparation 71, and the inconsequential changes were made using 3-(2,2-difluoro-6-hydroxy-1,3-benzodioxanthene). Alken-5-yl)-3-yl-1-yloxymethyl)-1,3-dihydro-2-indole-2-one substituted 3-(2,2-difluoro-6- Hydroxy-1,3- benzodioxanthene-5-yl)-3-hydroxy-1-{[5-(trifluoromethyl)furan-2-yl]nonyldi1,3-dihydrogen -2Η-indol-2-one, 3-(2,2-difluoro-6-hydroxy-1,3-benzodioxanthene-5-ylindole-methyl-1,3-di Hydrogen-2H-W哚-2-one (85%) as a colorless amorphous solid: 4 NMR (300 MHz, CDC13) &lt;5 7.47-7.40 (m, 1 Η), 7.37-7.31 (m, _ 1H ), 7.28-7.20 (m, 2H), 6.99 (d, J = 7.8 Hz, 1H), 6.85 (s, 1H), 6.60 (s, 1H), 5.10 (s, 1H), 3.25 (s, 3H) MS (ES+) m/z 320.1 (M + 1). Preparation 73 3-(2,2-difluoro-6-hydroxy-1,3-benzodioxol-5-yl)-l- Synthesis of {[3-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-dihydro-2H-M丨哚-2-one Α· 1-{[3-(trifluoromethyl) Acridine-2- Synthesis of methyl hydrazine·2,3·dione in lH-p?b--2,3-dione (2.08 g, 14.1 mmol) in anhydrous ν, Ν-dimethyl 143924- Sp-20091127-l -276- (8) 201020257 Cooled in methotrexate (40 ml) (〇.〇 solution, added sodium hydride (60% dispersion in mineral oil, U8 g, 29 6 mmol) And the resulting purple suspension was spoiled for 15 minutes at 0 C. In the suspension described above, 2-(Chloroindenyl)-6-(trifluoromethyl)p ratio salt was added via cannula. Acid salt (Li, j. w〇2〇〇6/ 34004) (3.27 g ' 14.1 mmol) in anhydrous n,N-dimethyl decylamine (2 mL) over a period of 10 min The reaction mixture was allowed to warm to ambient temperature 'stirring for 2.5 hours, and poured into brine (6 liters) and water (6 liters) cooled (0 C) and thoroughly mixed into the mixture. Suspension® sonic for 5 minutes, allowed to warm to ambient temperature, and filtered. Wash the filter cake with water (100 mL) and hexane (100 mL), air dry, and dry under high vacuum. {[3-(Trifluoromethylidinyl-2-yl)] Kib 1H-indole-2,3-dione (3.21 g, 74%), as an orange solid: iHNMR (3 〇〇 MHz CDCl3) occupies 859 (d, J = 48 Hz, 1H), 8.00 (d, J = 7.9 Hz, 1H), 7.65 (d, J = 7.9 Hz, 1H), 7.49-7.42 (m, 1H), 7.37-7.30 (m, 1H), 7.12-7.06 (m, 1H), 6.59 (d , J = 7.9 Hz, 1H), 5.24 (s, 2H) ; MS (ES+) m/z 307.3 (M + 1). ❹ B. 3-(2,2·Difluoro·6-hydroxy-1,3-benzodioxol.5·yl)-3-hydroxy-l-{[3-(trifluoromethyl) Synthesis of late pyridine-2-yl]fluorenyl}·ι,3-dihydro-2H-W哚-2-one according to the procedure described in Preparation 71Α and using irrelevant changes, 1-{[3 -(Trifluoromethyl)pyridine-2-yl]methyl b1Η_嘀哚_2,3_dione substituted 1-{[5-(trifluoromethyl)furan-2-yl]methyl}- 1沁吲哚-2,3-dione, 3-(2,2-difluoro-6-hydroxy-1,3-benzodioxanthene-5_yl) is obtained, each hydroxyl group is small {[3_( Trifluoromethyl)indol-2-yl]nonyldi1,3-1,3-hydrogen-2indole-2-one (32%), yellow-brown amorphous solid: MS (ES+) m/z 481 .2 (M+l). C· 3_(2,2-difluoro-6-hydroxy-13-benzodioxanthene·5-yl) is small {[3.(trifluoromethyl 143924-sp-2009l 127-1 •277· 201020257 Synthesis of &gt;pyridin-2-yl]fluorenyl}·ι,3·dihydro-2H•(9)哚_2· ketone According to the procedure described in Preparation 71Β, and irrelevant changes are used, 3- (2'2-difluoro-6-carbyl 4,3-benzodioxanthene-5)3hydroxy-1-{[3-(difluoroindolyl)-pyridyl-2-yl]曱基卜1&gt;3 dihydro 2Η_啕哚_2_one is substituted for 3-(2,2-difluoro-6-trans-yl-1,3-benzodioxolan-4-yl) Hydroxy_丨丨[5_(trifluoromethyl)furan-2-yl]indenyl}4,3·dihydro-2H, 哚_2-one, 3 (2,2-difluoro-6-hydroxy- 1,3-benzodioxanthene each) small {[3_(trifluoromethyl)pyridine_2_yl]methyl 1,3-dihydro-2H-indol-2-one (91% ), as a colorless amorphous solid: MS (ES+) m/z 465.2 (M + 1). Preparation of 74 6-(diphenylmethyl)-8-(6-hydroxy-2,3-dihydro-1 -Synthesis of benzofuran-5-yl)-2,3,6,8-tetrahydro-7H-[1,4]dioxolylene[2,3-f]indole-7-_ · 6·(diphenylfluorenyl).2,3«dihydro-6Η-[1,4]dioxanthene[2,3〇吲哚-7,8.dione Synthesis of 2,3-dihydro-6H-[1,4]dioxolyl-[2,3-f]indole-7,8-dione (Lackey and Stembach, PCT, 1993: 993 -997) (1.73 g, 8.42 mmol) in anhydrous N,N-didecylguanamine (28 ml) cooled ((rc) solution, added sodium hydrogen fude (60% in the mine) In the oil, 〇·37 g, 9.26 mmol.) The mixture was stirred at ambient temperature for 1 hour, and bromodibenzopyrene (2.39 g, 9.69 mmol) was added. After stirring at ambient temperature for 16 hours. Additional bromodipodane (0.42 g, 1.68 mmol) was added. The mixture was taken at ambient temperature for 8 hours then diluted with water (200 mL) and ethyl acetate (200 mL). The layers were extracted with ethyl acetate (2×100 mL). EtOAcjjjjjjjjjjjjjjjjj 201020257 Concentrate in vacuo. Purify the residue by column chromatography, elute with ethyl acetate in a 35% to 50% gradient of hexane to give 6-(2)-dihydro- 611-[1,4 Dioxodecene-[2,3-f]indole-7,8-dione (0.7 g, 22%) as a red solid: iHNMR (300MHz, CDC13) 5 7.41-7.28 (m, 10H) ,7,16(s,lH), 6.94-6.91 (m, 1H), 5.96 (s, 1H), 4.27-4.14 (m, 4H); MS (ES+) m/z 371.9 (M + 1). B. 6-(Diphenylfluorenyl)-8-carbyl-8-(6-hydroxy-2,3-dihydro-1·benzop-amyl-5)yl 2,3,6,8 - Synthesis of tetrahydro-7-[1,4]dioxolene and b-7-one according to the procedure as described in Preparation 2A, and insignificant changes, using 2,3-dihydrobenzene And furan_6-alcohol replaces 3-bromophenol, and uses 6-(diphenylmethyl)_ 2,3-hydrogen-6H-[1,4]dioxygen ortho[2,3_η吲嗓_ Substitution of 7,8-dione to 1-((5-(trifluoromethyl)pyran-2-yl)methyl)indoline-2,3-dione to give 6 (diphenylmethyl)- 8-hydroxy-8-(6-hydroxy-2,3-dihydrobenzobenzofuran-5-yl)-2,3,6,8-tetrahydro-7Η-[1,4]dioxanthene And 吲哚7-ketone (94%) as a colorless solid: MS (ES-) m/z 506·1 (Μ -1). C· 6-(diphenylmethyl).8-(6-hydroxy.2,3-dihydro-1·benzofuran·5-yl)·2,3,6,8·tetraar-7Η·[ 1,4]Dioxeremene [2,3 synthesis of 5丨哚.7-ketones will be 6-(diphenylfluorenyl) each hydroxyl group_8_(6-hydroxy-2,3-dihydrobenzobenzene And furan_5_yl)-2,3'6,8-tetrahydro-7Η-[1,4]dioxoisen[2,3-f]indole-7-one (0.78 g, 1.5 m A mixture of triethyl decane (1.2 mL) and trifluoroacetic acid (12 mL) in dichloromethane (1 mL) was stirred for 1 hour at TC then 1 hour at ambient temperature. The mixture was concentrated in vacuo to give crude 6(diphenylmethyl)-8-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)·2,3,6,8 -tetrahydro-7Η-[1,4]dioxolysine[2,3_handle_7-ketone (1〇〇%): Ms(10) 十)心4921 143924-SD-20091127-1 201020257 ( Μ + 1) 〇Preparation 75 1♦Transyl-2,3-dihydro-1-benzofuran-5-yl)-3-(4-methoxybenzyl)-indole, 3-dihydro-2Η -ρ比洛和[3,2-f&gt;The synthesis of chalcone-2-one A. 3-(4-methoxybenzyl).iH_p is more than 并阳阳奎奎·以姐)·: Ketone Synthesis at ambient temperature '1H-pyrrolo[3,2-f Quinoline-l,2(3H)-dione (Bmmson, Η. Ν· et al., /. Med C/iem. 2001, 44(25): 4339-4358) (0.15 g, 0.76 mmol) Sodium hydride (60% in mineral oil, 4 g in mineral oil, 〇98 mmol) was added to the stirred solution in anhydrous N,N-dimethyl decylamine (1 mL). The mixture was stirred at ambient temperature for a few hours and 4-methoxybenzyl bromide was added (0.16 mL &lt;RTI ID=0.0&gt;&gt; The mixture was diluted with EtOAc (1 mL). EtOAc (EtOAc m. The residue was purified by column chromatography and eluted with a gradient of 50% to 65% of ethyl acetate in hexane to give 3-(4-methoxyhanylpyrho[3,2 -f&gt; 奎琳-1,2(3H)-二_ (0.20 g, 82%), as a red solid: Ms (es+) m/z 319.0 (Μ + 1) 〇C· 1 hydroxy·1·(6 · hydroxy·2,3-dihydro-indole benzofuran _5_yl)_3_(4·decyloxybenzyl)-1,3-dihydro-2Η-pyrrolo[M-fj porphyrin·2, The synthesis was carried out according to the procedure described in Preparation 2, and the insignificant changes were made, using 2,3-dihydrobenzofuran·6·ol to replace 3-bromophenol, and using decyloxybenzyl)H. [3,2·Xiaokuiling],) Diketone replacement 1 ((5 (three said methyl oxime-2-yl) Methyl) dihydrogen + doododone, obtained [small base (6_base 2, 3_two 143924-SP-20091127-1 -280- 201020257 hydrogen-1-benzofuran-5-yl) -3-(4-methoxybenzyl H,3_dihydro-neu-pyrrolo[3,2-f]Junlin-2-_ (58%), colorless solid: Ms (ES+) - you 〇^. D. 1-(6-hydroxy-2,3-dihydro-1. benzofuran-5_yl)_3_(4methoxybenzyl hydrazine, 3 dihydro-2-indole-dehydrazino[ Synthesis of 3,2-f]u Kui u Lin-2- Ming According to the procedure as described in Preparation 74C, and irrelevant changes were made, 1-hydroxy-H6-hydroxy-2,3-dihydrobenzobenzene was used. Furan:yl)_3 (4_nonyloxyindenyl)-1,3-dihydro-2H-pyrrolo[3'2-f]quinolin-2-one to replace 6-(diphenylmethyl)-hydroxyl group 8-(6-Hydroxy-2,3-dihydro-1-benzofuran·5-yl^, from the four-hydrogen terpenes (4) di-oxodecene [2,34吲哚_7-one, Obtaining H6-hydroxy-2,3-dihydrobenzobenzopyran-5-yl)-3-(4-methoxybenzyl H,3-dihydro-2H-pyrrolo[3,2f]quinoline 2-辋 (37%), as colorless solid: MS (ESI+) m/Z 438.9 (M+l). Preparation 76 2,4-dihydroxy-5-[l-(4-methoxybenzyl) Synthesis of _2_keto-2,3-dihydro-1H-indol-3-yl]benzonitrile Synthesis of 2,4-dihydroxy·Η3·hydroxyl small (4-methoxybenzyl).2-keto-2,3_dihydro·ιη·©啕哚-3-yl]benzonitrile At 2C, 2,4-dihydroxybenzonitrile (4.33 g, 321 mmol) in tetrahydropyran (50 ml) and 1,2-dichloroethane (4 ml) To the mixed solution, isopropylmagnesium hydride (17.7 ml, 2 Torr from tetrahydrofuran, 35.4 mmol) was added. The mixture was stirred at 〇〇C for hrs and at ambient temperature for 2 hours, and K4_decyloxybenzyl hydrazone 2,3dione (8 g, 32.1 mmol) was added to the reaction mixture. . The mixture was stirred under reflux for 18 hours, cooled to 〇t, and added M 5% v/v hydrochloric acid. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo 143924-SP-20091127-1 -281- 201020257. The residue was subjected to column chromatography and eluted with ethyl acetate/hexane (1/1) to give 2,4-dihydroxy-5-[3-hydroxy-1-(4-methoxybenzyl) )-2-keto-2,3-dihydro-1H-indol-3-yl]benzonitrile (10.30 g, 79%): 4 NMR (300 MHz, DMSO-d6) δ 10.81 (s, 1H ), 10.35 (s, 1H), 7.80 (s, 1H), 7.32 (d, J = 9.0 Hz, 1H), 7.14-7.08 (m, 1H), 6.88-6.84 (m, 4H), 6.75-6.72 ( m, 1H), 6.63 (s, 1H), 6.30 (s, 1H), 4.79 (ABq, 2H), 3.70 (s, 3H); MS (ES+) m/z 384.8 (M-17). B. Synthesis of 2,4-dihydroxy-5[1-(4-decyloxyindenyl)-2-keto-2,3-diar-argon-1H-indol-3-yl]benzonitrile 2,4-Dihydroxy-5-[3-hydroxy-1-(4-decyloxybenzyl)-2-keto-2,3-dihydro-1H-indol-3-yl]benzonitrile (10.3 g, 25.5 mmol) and triethyl decane (12.3 mL, 77.0 mmol) in a stirred suspension of dichloromethane (1 mL), trifluoroacetic acid (1 〇. ML, 129 millimoles). The reaction mixture was stirred at ambient temperature for 18 h and concentrated in vacuo. The residue was triturated in hexanes to give 2,4-dihydroxy-5-[l-(4-methoxyindolyl)-2-one-2,3-dihydro-1?-indole- 3-yl]benzonitrile (9.70 g, 98%): mp 162-163°C (hexanes); 1H NMR (300 MHz, CDC13) (5 10.84 (s, 1H), 10.47 (s, 1H), 7.39 (s, 1H), 7.28 (d, J = 9.0 Hz, 2H), 7.13-7.08 (m, 1H), 6.93-6.78 (m, 5H), 6.43 (s, 1H), 5.72 (s, 1H) , 4.92-4.73 (m, 3H), 3.69 (s, 3H); MS (ES+) m/z 386.9 (M + 1). Preparation 77 2-fluoro-4-hydroxy-5-[l-(4- Synthesis of methoxybenzyl)-2-keto-2,3-dihydro-1H-indol-3-yl]benzonitrile A· 2-fluoro-4-hydroxy-5-[3·hydroxyl Synthesis of -1-(4-methoxybenzyl)-2·keto-2,3·dihydro 143924-SP-20091127-1 -282- 201020257 -1H4嗓-3_yl]benzonitrile C under stirring of 2-fluoro-4-tetrahydroxybenzonitrile (8.00 g, 58.3 mmol) in 1'2-dioxaethane (5 mL) and tetrahydrofuran (5 mL) Add isopropyl magnesium chloride (292 ml, 2 〇M solution in tetrahydrofuran '58.4 mmol) in solution. Stir the mixture at 〇 °c for 1 hour at ambient temperature 2 hours. Add 1-(4-methoxybenzyl)-m 哚 哚 2,3 diketone (15 gram '56.1 mmol) and the reaction mixture was stirred for 156 hours under reflux. To 〇 ° C, and add 1% w/v hydrochloric acid. Separate the liquid phase and extract the aqueous layer with trichloromethane (100 ml). The combined organic extracts are washed with water and brine. Dehydration and drying, and filtration. The filtrate was condensed in a vacuum. The residue was subjected to column chromatography and eluted with ethyl acetate/hexane (1A) to give 2-fluoro-4-hydroxy-5-[ 3-Hydroxy-1-(4-methoxybenzyl)-2-keto-2,3-dihydro-1H-indol-3-yl]benzonitrile (12.30 g, 54%): 1H NMR (300 MHz, DMSO-d6) δ 8.05 (d, J = 9.0 Hz, 1H), 7.34-7.32 (m, 2H), 7.17-7.11 (m, 1H), 6.91-6.76 (m, 7H), 4.78 ( ABq, 2H), 3.72 (s, 3H) ; MS (ES+) m/z 404.9 (M + 1 Β·························· Synthesis of 2-_yl-2,3·dihydro-1H·峋哚-3·yl]benzonitrile to 2-fluoro-4-hydroxy-5-[3-carbyl-1-(4-methyl) Oxybenzyl) 2 keto '3-dihydro-indole-Mh-3-yl}benzonitrile (12.0 g, 29.7 Mole) 'stirring 88.9 mmol) and the suspension was the added trifluoroacetic acid (1〇 milliliters' in triethyl Silane (14.2 mL 129 mmol). The reaction mixture was stirred at ambient temperature for 168 hrs and concentrated in vacuo. The residue is recrystallized from ethyl acetate/hexane to give 2-fluoro-4-hydroxy-5-[l-(4-methoxybenzyl)-2-one-2,3-dihydro · 1H_&lt; 143924-sp*20091127-l -283 · 201020257 哚-3-yl]benzonitrile (10.5 g '90%): 4 NMR (300 MHz, CDC13) δ 131-1.\2 (m, 7Η ), 6.94 (d, J = 6.0 Hz, 1H), 6.85-6.79 (m, 3H), 5.07 (s, 1H), 4.88 (ABq, 2H), 3.75 (s, 3H) ; MS (ES+) m/ Z 388.9 (M + 1). Preparation 78 3-(5-Pyridyl-3-indolyl-1,2-benzoisoindole-6-yl)-1-(4-decyloxy)-1,3-dihydro-2H Synthesis of 3-indole-2-one. A. 3-Phenyl-3-(5-carbyl-3-indolyl-1,2-benziso-sal-6-yl)-1-(4- Synthesis of methoxyl group)-1,3·dihydro-2Η-»»5丨嗓-2- ing at 0C' in 3-methyl-1,2-benziso, s--5-alcohol (Lindemann et al. _ Justus Liebigs Annalen der Chemie 1927, 456: 308) (3.10 ^ &gt; 20.8 ^ % ear) in a stirred solution of 1,2-dichloroethane (200 ml), isopropyl Magnesium vapor (10.4 ml, 2.0 M solution in tetrahydrofuran, 20.8 mmol). The mixture was stirred at 0 °C for 1 hour and then at ambient temperature for 2 hours. 1-(4-Methoxybenzyl)-indole-theta, a-2,3-di-form (5.3 g, 19.8 mmol) was added, and the reaction mixture was stirred under reflux for 120 hr. The mixture was cooled to 〇 ° C ' and 5% w/v hydrochloric acid was added. The organic phase was separated, washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. Ο The residue is subjected to column chromatography to dissolve in ethyl acetate/hexane (18) to give 3-hydroxy-3-(5-hydroxy-3-methyl-l,2-benziso'^唆-6-yl)-1-(4-methoxyindenyl)-1,3-dihydro-2Η-ρ5| p-butanone (0.87 g '10%) : NMR (300 MHz, DMSO -d6) δ 9.68 (s, 1Η), 8.01 (s, 1H), 7.37-6.76 (m, 10H), 4.83 (ABq, 2H), 3.70 (s, 3H), 2.46 (s, 3H); MS ( ES+) m/z 415.0 (M - 1). B. 3-(5-Pyryl-3-methyl-1,2·benzoisoindol-6-yl)-1-(4-methoxybenzyl)-1,3-dihydro-2H- Synthesis of 吲哚-2·ketone 143924-SP-20091127-1 • 284· (S) 201020257 on 3-carbyl 3-(5-hydroxy-3-methyl-1,2- benzoxazole 6·yl)small (4-methoxybenzyl)_1'3~dihydro-2H-indol-2-one (0.84 g; 2.0 mmol) in triethyl decane (3.0 ml, 18_7 mmol) Trifluoroacetic acid (15,0 ml) was added to the stirred suspension in the ear. The reaction mixture was at 5 Torr. The mixture was stirred for 26 hours, allowed to cool to ambient temperature and concentrated in vacuo. The residue is recrystallized from ethyl acetate / hexane to give 3-(5-hydroxy-3-indolyl·u_benzisoxazole-6-yl) small... methoxy-aryl)-1,3- Dihydro-2H-indol-2-one (0.74 g, 92%): 1 η NMR (3 〇〇 MHz, CDC13) (5 7-34-6.80 (m, 10H), 5.29 (s, 1H), 4.87 (ABq, 2H), 3.74 (s, ® 3H), 2.45 (s, 3H); MS (ES+) m/z 400.9 (M + 1) Preparation 79 4-bromo-3-(7-hydroxy- Synthesis of 2,3-dihydro-1,4-benzodioxanthene) small methyl-1,3-dihydro-2H-M丨哚-2-one A. 4-bromo group. 1. The synthesis of 曱i_ih-p5-dot-2,3-dione at ambient temperature was brewed in 4-Niche base (90.4 g, 400 mmol) in N,N_ dimercapto To a stirred solution of the amine (400 mL) was added EtOAc (196.0 g, &lt;&lt;&gt;&gt; The mixture was stirred for 18 hours at ambient temperature. The solid was removed by filtration, the filtrate was concentrated in vacuo, and the residue was purified in water and washed with diethyl ether to give 4-bromo-decyl-1H_P 3-dione (82.0 g, 85%): 1H NMR (300 MHz, DMSO-d6) occupies 7.95-7.89 (m, 1H), 7.68-7.64 (m, 1H), 7.53-7.49 (m, 1H), 3.50 (s, 3H). B. 4-Aki- 3-carbyl-3-(7-transyl-2,3·dihydro-1,4-benzodioxanthracene-6-yl)·1-methyl-1,3·dihydro-2Η · Synthesis of «»5丨嗓·2·嗣 at 2 °C in 2,3-dihydro-1,4-benzodioxanthene-6-ol (36.0 g, 230 143924-sp-20091127 -l -285· 201020257 millimolar) In a stirred solution of di-methane (1000 ml), add isopropyl gasification town (120 ml, 2.0 M solution in tetrahydrofuran, 240 mmol) The mixture was stirred at 〇 ° C for 1 hour, and 4-bromopyridinyl-1H_ 啕哚-2,3-dione (48.0 g, 200 mmol) was added. The reaction mixture was taken at ambient temperature. After stirring for 22 hours, 5% w/v hydrochloric acid was added under TC. The organic layer was separated, washed with water and brine, dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo and the residue was It is prepared in methylation and washed with diethyl ether to give 4-bromo-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxan-6-yl )-1-methyl-1,3 -Dihydro-2H-noise-2-嗣 (63.4 g, 80%): 1 H NMR (300 MW, DMSO-t^) δ 8.80 (s, 1H), 7.21-7.13 (m, 2H), 7.1. (m, 2H) 17), 375.8 (M-17). C. 4-bromo-3-(7.hydroxy-2,3·dihydro-1,4-benzodioxanthene·6·yl)-i•indenyl-1,3-diaza- Synthesis of 2Η_ρ5丨嗓-2-嗣 at 〇°C' in 4-bromo-3-hydroxy-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6- Base)-1-methyl-1,3-dihydro-2H-indol-2-one (61.0 g; 155 mmol) with triethyldecane (75·0 ml '456 mmol) in two Trifluoroacetic acid (48 ml, 623 mmol) was added to the stirred solution of gas hexane (3 mM). The reaction mixture was stirred at ambient temperature for 2 hrs and concentrated in vacuo. The residue was triturated in methanol and washed with diethyl ether to give 4-bromo-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxolene-6-yl )+Methyl^yi-dihydro-2Η-indol-2-one (57.0 g '97%): 4 NMR (300 MHz, CDC13) 5 7.31-7.17 (m, 3H), 6.87-6.83 (m, 1H) ), 6.62 (s, 1H), 6.17 (s, 1H), 4.97 (s, 1H), 4.22-4.08 (m, 4H), 3.18 (s, 3H) ; MS (ES+) m/z 376.1 (M + 1), 378.1 (M + 143924-sp-20091127-l -286- (8) 201020257 1). Preparation of 80 6-methyl-8-(2-nitrophenyl)-7-keto-2,3,7,8-tetrahydro-6H-[1,4]dioxanthene [2, Synthesis of 3-f]indole-8-carboxylic acid methyl ester A·6-methyl-2,3-dihydro-6Η·[1,4]dioxene terpene [2,3-fH b Synthesis of -7,8-dione according to the procedure described in Preparation 79A, and irrelevant changes were made using 2,3-dihydro-6H-[1,4]dioxene terpene [2, 3-f]啕哚-7,8-dione displaces 4-® bromoindole to obtain 6-methyl-2,3-dihydro-6H-[1,4]dioxene terpene [ 2,3-f] (s, 1H), 4.41-4.38 (m, 2H), 4.27-4.24 (m, 2H), 3.08 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ ; MS (ES+ ) m/z 220.2 (M + 1). B. Synthesis of 6-methyl-2,3,6,8-tetrahydro-7Η·[1,4]dioxanthene[2,3-fH丨哚-7-one to 6-methyl -2,3-dihydro-6H-[1,4]dioxolynene [2,3-fH哚-7,8-dione (3.00 g '13.7 mmol) in 1,4-two In a solution of oxetam (25 ml), hydrazine monohydrate (25 ml) was added. The reaction mixture was stirred at reflux for 4 h, then cooled to EtOAc EtOAc. The mash was concentrated in vacuo. The residue was recrystallized from ethyl acetate/hexane to give 6-methyl-2,3,6,8-tetrahydro-7H-[1,4]dioxolene [2,3-fH哚-7-ketone (2.46 g, 87%): iH NMR (300 MHz, CDC13) δ 6.75 (s, 1H), 6.49 (s, 1H), 4.19-4.12 (m, 4H), 3.36 (s, 2H ), 3.00 (s, 3H); MS (ES+) m/z 206.2 (M + 1). C. 6-Methyl-8-(2-nitrophenyl)-2,3,6,8-tetrahydro-7H-[1,4]dioxanthine and 143924-sp-20091127-1 - 287- 201020257 [Synthesis of 2,3-fH丨嗓-7-ketone at 6 °C, 6-mercapto-2,3,6,8-tetrahydro-7H-[1,4] dioxane Addition of sodium hydride (in the mine) in a stirred solution of terpene and cation-anthraquinone-7-one (1.03 g, 5.01 mmol) in hydrazine, hydrazine dimethyl dimethyl carbamide (1 mM) 6% w/w dispersion in oil, 0.26 grams, 6.5 millimoles). The reaction mixture was stirred at 〇 ° C for 3 ' '' 1-fluoro-2- benzene benzene (〇. 7 〇 ml '6.6 mmol), and the mixture was spit at 18 ° C for 18 hours. 1% w/v hydrochloric acid (1 mL) was added below and the mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate, and filtered. The sputum was concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate /hexane (1/2) to give 6-methyl-8-(2-nitrophenyl)-2,3,6,8 -tetrahydro-7H-[1,4]dioxoisen[2,3-f]indole-7-one (0.41 g, 24%): 1H NMR (300 MHz, CDC13) δ 8.05-8.01 (m, 1H), 7.58-7.51 (m, 1H), 7.49-7.42 (m, 1H), 7.23-7.19 (m, 1H), 6.69 (s, 1H), 6.45 (s, 1H), 5.28 (s , 1H), 4.28-4.18 (m, 4H), 3.21 (s, 3H). D·6-Methyl-8·(2-nitrophenyl)-7-keto-2,3,7,8-tetrahydro-6H-[1,4]dioxolysine [2, Synthesis of 3-fH丨嗓-8-carboxylic acid methyl ester β at 6°〇, in 6-mercapto-8-(2-nitrophenyl)-2,3,6,8-tetrahydro-7 Adding lithium bis(trimethyldecylalkyl) to a stirred solution of hydrazine [1,4]dioxantimin-7-one (0.40 g, 1.2 mmol) in tetrahydrofuran (1 mL) Amine (1.0 M solution in tetrahydrofuran, 1.5 mL, 1.5 mmol). The reaction mixture was stirred at 0&lt;0&gt;C for 10 min then EtOAc (EtOAc &lt Here. (: 10% w/v hydrochloric acid (5 ml) was added, and ethyl acetate (3×50 ml) was used to extract and mix -288 - 143924-sp-20091127-1 (S) 201020257. The combined organic extracts were combined. Washed with water and brine, dried over anhydrous sodium sulfate, and filtered, and then filtered and evaporated. 6-fluorenyl_8-(2-nitrophenyl)-7-keto-2,3,7,8-tetrahydro-611-[1,4]dioxene terpene [2,3_£ ^Budu-8-carboxylate (0.21 g, 44%): iHNMR (300MHz, CDCl3) 5 7,92-7.89 (m, 1H), 7.48-7.37 (m, 2H), 7.20-7.19 (m , 1H), 6.97 (s, 1H), 6.41 (s, 1H), 4.21.4.14 (m, 4H), 3.65 (s, 3H), 3.12 (s, 3H). Preparation 81

4-bromo-1-(diphenylindenyl)-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanene)-1,3-dihydro- Synthesis of 2H-W p-butanone A. 4. Synthesis of bromodiphenylmethyldihydro-4-pto-2,3-diindole according to the procedure as described in Preparation 26A, and carrying out irrelevant changes Substituting 4-bromoindole for 2,3-dihydro-6H-[1,4]dioxanthene [2,3-fH| 哚-7,8-dione, and using bromo Diphenylmethane was replaced by 2_(bromomethyl)_5_(trifluoromethyl), and 4-bromo-diphenylmethyldihydrooxan-2,3-dione (78%) was obtained as a red solid: MS (ES+) m/z 413.8 (M + 23), 415.8 (M + 23). Β· 4-Bromo-1-(diphenylmethyl)-3-hydroxy_3-(7-hydroxy·2,3 dihydro·^benzodioxan-6-yl)-1,3 Synthesis of dihydrogen.2Η·吲哚_2&gt;_ According to the procedure described in Preparation 2Α, and irrelevant changes were made, 2,3-dihydro-1,4-benzodioxene terpene was used. _6_Alcohol replaces 3-bromophenol, and replaces 1 (5•(trifluoromethyl)-propan-2- with 4_bromo-1-diphenylmethyldihydroindole_2,3-dione Dihydroquinoline 2,3-dione, 4-(bromo)di(diphenylmethyl)_3_hydroxy-3-(7-trans-yl-2'3-dihydro-l, 4-benzodioxolysene _6_yl) 13_ dihydro 2 Η 啕 -2--2-one (99%), colorless solid:! H NMR (3〇〇丽2, DMS〇d6) accounted for 143924-sp-20091127-l 201020257 9.06 (s, 1H), 7.44-7.28 (m, l〇H), 6.98-6.82 (m, 2H), 6.68 (s, 1H), 6.33 (d, J = 7.4 Hz, 1H), 6.16 (s, 1H), 4.23-4.08 (m, 4H) ; MS (ES+) m/z 566.1 (M + 23), 568.1 ( M +23). C· 4-bromo-1((diphenylmethyl)_3_(7_transyl 2,3·dihydro-i,4_benzodioxanthene-6-yl)-1,3_ Synthesis of dihydroproton-2-_ according to the procedure as described in Preparation 4C, and irrespective changes were made using 4-bromo-1-(diphenyl)-3-yl-3-yl ( 7-Hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3-dihydro-2H-indol-2-one substituted 4-alkyl-1 -(Diphenylmethyl)-3-carbyl-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1,3-dihydro-2H-W _ 哚2-ketone, 4-bromo-1-(diphenylfluorenyl)- 3 hydroxy-2,3-dihydro-I,4-benzodioxene-6-yl)-1,3 -Dihydro-2H-indol-2-one (86%): as a yellow solid: NMR (300 MHz, DMSO-d6) 5 9.05 (s, 1H), 7.42-7.28 (m, l〇H), 6.98 -6.87 (m, 3H), 6.68 (s, 1H), 6.33 (d, J = 7.6 Hz, 1H), 6.16 (s, 1H), 4.22-4.16 (m, 4H) 〇 Preparation 82 1-(diphenyl Mercapto)-4-fluoro-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3-dihydro-2H-indole Synthesis of 2-ketone® Α· 1-(Diphenylmethyl)_4_Waki-1H-»»Synthesis of 嗓-2,3-dione from 1-(1 methyl)-3-硪Radyl-4-fluoro-based p-bud (8.85 Grams, 20.7 mmol.) In a solution of a mixture of acetonitrile (25 ml) and water (5 ml), bismuth(III) chloride monohydrate (〇.3 g, 1.45 mmol) was added. Sodium iodate (13.3 g, 62.2 mmol). The reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was diluted with ethyl acetate (100 ml), washed with water (3·25 ml), saturated aqueous ammonium carbonate (3×25 ml) and brine (3×25 ml) with anhydrous sulfur 143924-sp-20091127-1 (S ) 201020257 Sodium dehydration drying 'filtered and concentrated in vacuo. The residue was crystallized from acetonitrile to give 1-(diphenylhydrazinyl)-4-fluoro-1H-W?-2,3-dione (1.73 g, 25%) as an orange solid: m. 171. (: ; 1HNMR (300MHz, DMSO-d6) (5 7.49-7.41 (m, 1H), 7.38-7.28 (m, 10H), 6.86 (dd, J = 8.8, 8.8 Hz, 1H), 6.80 (s, 1H ), 6.45 (d, J = 8.1 Hz, 1H); 13 C NMR (75 MHz, DMSO-d6) δ 178.3, 157.8, 157.7 (d, 261.0 Hz), 150.6 (d, 3JC_F = 6.0 Hz), 139_7 ( d, 2JC-F = 10.0 Hz), 137.0, 128, 5, 128.3, 127.8, 110.7 (d, 2JC-F = 19.5 Hz), 108.8 (d, 4 JC.F = 2.9 Hz), 106.4 (d, 3 JC.F = 18.2 Hz), 28.7; MS (ES+) m/z ® 332.2 (M + 23). Β· 1-(Diphenylmethyl)_4-fluoro-3-hydroxy-3-(7-hydroxyl) Synthesis of -2,3-dihydro-1,4-benzodioxanthene-6-yl)_1,3-dihydro-2H-V?丨哚-2.one as described in Preparation 1A Procedure, and insignificant changes, using 2,3-dihydrobenzo[b][l,4]dioxanthene-6-ol to replace 2-mercaptobenzo[d] «•serazole -5-alcohol, and replacing the hydrazine with 1-(diphenylmethyl)-4-1yl-1H-indole-2,3-dione to obtain 1-(diphenylmethyl)-4-fluoro 3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3-dihydro-2H-indole-2 -ketone (83%) as colorless solid: mp 209-211 ° C (dec. 1H NMR (300 MHz, DMSO-d6) 5 9.15 (s, 1H), 7.43-7.27 (m, 11H), 7.01 (ddd, J = 8.2, 8.2, 5.9 Hz, 1H), 6.87 (s, 1H) ), 6.79 (s, 1H), 6.61 (dd, J = 8.8, 8.8 Hz, 1H), 6.21 (s, 1H), 6.16 (d, J = 7.9 Hz, 1H), 4.25-4.14 (m, 4H) 13C NMR (75 MHz, DMSO-d6) δ 176.2, 157.9 (d, 248 Hz), 147.1, 145.0 (d, 3JC-F = 8.7 Hz), 142.7, 137.7 (d, 2JC.F = 30.9 Hz), 135.4, 130.1 (d, 3Jc.f = 8.7 Hz), 128.4 (d, 3JC-F = 13.9 Hz), 128.3 (d, 3 JC.F = 8.4 Hz), 127.5 (d, 3JC_F = 11.9 Hz), 119.4 , 117.9 (d, 2JC-F = 18.9 Hz), 116.1, 109.3 (d, 2Jc-F = 20.3 Hz), 107.2 (d, 4JC.F = 2.1 143924-sp-20091127-1 -291 - 201020257

Hz), 103.1, 73.0, 64.2, 63·7, 57·5; MS (ES+) m/z 506.0 (Μ + 23). C· 1-(diphenylfluorenyl)-4fluoro-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6·yl)·1,3- Synthesis of dihydro-2Η-indol-2-one in 1-(monomethyl)-4-fluoro-3-carbo-3-(7-trans- 2,3-dihydro-1,4 -benzodioxanthene-6-yl)-1,3-dihydro-2H-W哚-2-one (1·74 g, 3.60 mmol) in dioxane (40 ml) Trifluoroacetic acid (1.64 g, 14.4 mmol) and triethyl decane (1.68 g, 14.4 mL) were added to the solution. The reaction mixture was stirred at ambient temperature for 16 hours, and concentrated in vacuo. EtOAc was purified eluting EtOAc EtOAc EtOAc 3-(7-transyl-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3-dihydro-2H-indol-2-one 1.54 g, 92%), as a colorless solid: m.p.: 115-118 〇C; 1H NMR (300 MHz, DMSO-d6) (5 9.17 (s,lH), 7.42-7.26 (m, 11H), 7.01 (ddd, J = 8.2, 8.2, 5.9 Hz, 1H), 6.91 (s, 1H), 6.67 (dd, J = 8.8, 8.8 Hz, 1H), 6.27 (s, 1H), 6.23 (d, J = 7.9 Hz, 1H ), 4.99 (s, 1H), 4.20-4.14 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) 5 176.2, 157.9 (d, 1 Jc - F = 248 Hz), 147.1, 145.0 (d , 3JC.F= 8.7 Hz), 142.7, 137.7 (d, 2JC.F= 30.9 Hz), 135.4, 130.1 (d,3JC_F= 8.7 Hz), 128.4 (d, 3JC-F=13.9 Hz), 128.3 (d ,3JC-F= 8.4 ❹

Hz), 127.5 (d, 3Jc.f = 11.9 Hz), 119.4, 117.9 (d, 2JC.F = 18.9 Hz), 116.1, 109.3 (d, 2 JC.F = 20.3 Hz), 107.2 (d, 4 Jc -F=2.1 Hz), 103.1, 73.0, 64.2, 63.7, 57.5; MS (ES+) m/z 467.9 (M + 1) Preparation 83 H4-fluorophenyl)-3-(7-hydroxy-2,3- Synthesis of di-n-1,4-benzodioxanthene,yl-l,3-dihydro-2H-MIindol-2-one A. 1-(4-Fluorophenyl)-3-hydroxyl -3·(7·hydroxy-23-dihydrobenzodioxanthene 143924-sp-20091127-l -292- (8) 201020257 -6-yl)-l,3-dihydro·2Η-β卜朵- 2. The synthesis of ketones and the implementation of irrelevant changes,

Hydrogen-2H-eucalin-2-one (23%) 'is a beige solid: melting point 195_2〇〇〇c; 丨H nmr (300 MHz, DMSO-d6) δ 7.12 (s, 1H), 7.47-7.41 (m, 4H), 7.26 (s, 1H), according to the procedure as described in Preparation 1Α, and using 2,3-dibenzobenzo[b][i,4]dioxane 圜-5 -Alcohol, and using 1-(4-fluorophenyl)dihydrop #环/6 Xue Weng 1987, (24) : 1249) Settray® 7.21-7.16 (m,1H), 7.01-6.93 (m, 2H ), 6.68 (d, J = 7.8 Hz, 1H), 6.63 (s, 1H), 6.14 (s, 1H), 4.23-4.14 (m, 4H); 13C NMR (75 MHz, DMSO-d6) (5 176.3 , 160.9 (d, 1JC.F= 245 Hz), 147.1, 143.9, 142.6, 135.6, 132.0, 131.2 (d, JC-f= 2-9 Hz), 128.6 (d, 3JC.F= 8 Hz), 124.0 , 122.4, 121.2, 116.4 (d, 2 JC-f = 22.8 Hz), 115.1, 108.2, 103.4, 74.4, 64.3, 63.7, 57.2; MS (ES+) m/z 390.0 (M + 1). Β·1· (4-fluorophenyl)-3-(7-hydroxy_2,3·dihydro-1,4·benzodioxanthene-6·yl)-1,3_dihydro.211-4丨嗓-2·Synthesis of steel According to the procedure as described in Preparation 82C, and irrelevant changes were made, 1-(4-fluorophenyl)-3-carbyl-3-(7-hydroxy-2,3) was used. -dihydro-1,4- And dioxodecene-6-yl)-1,3-dihydro-2Η-indol-2-one replaces 1-(diphenylindenyl)-4-fluoro-3-hydroxy-3-(7 -hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3-dihydro-2-indole-2-one, 1-(4-fluorol) Phenyl)-3-(7-transyl-2,3-dihydro-1,4-benzodioxanthene-6-yl)-1,3-dihydro-2Η-吲哚-2- Ketone (59%) as colorless solid: 4 NMR (300 MHz, DMSO-d6) δ 9.16 (s, 1 Η), 7.51-7.39 (m, 4H), 7.17 (dd, J = 7.6 Hz, 7.6 Hz, 1H ), 7.05-6.96 (m, 2H), 6.67 (s, 1H), 6.68 (d, J = 7.8 Hz, 1H), 143924-sp-20091127-1 -293- 201020257 6.27 (s,1H), 4.84 ( s, 1H), 4.19-4.12 (m, 4H): MS (ES+) m/z 378.2 (Μ + 1). Preparation 84 Synthesis of 4-(azepine-decyl)-1-fluoro-2-methoxybenzene to (4-fluoro-3-methoxyphenyl)nonanol (Claudi et al., j Med Chem 199 〇) , 33(9): 2408) (0.90 g, 5.76 mmol) in the anhydrous liquid dioxane (1 mL) in the solution of the solution "Adding a chaotic sulfuric acid (0.84 ml, 12 mmol) and Anhydrous N,N-monodecylamine (2 drops). The reaction mixture was stirred at ambient temperature for 16 hours and concentrated in vacuo to give &lt;RTI ID=0.0&gt;&gt; NMR (300 MHz, CDC13) 5 7.05-6.86 (m, 3H), 4.53 (s, 2H), 3.88 (s, 3H). Preparation of 85 2-(lacylmethyl)-3,5-difluorop ratio bite hydrochloride synthesis in (3,5-difluoropyridin-2-yl)methanol (Almedia et al., w〇〇8/ 117〇5〇) (215 g, 14.8 mmol) in a solution of di-methane (2 mL), under which N,N-dimercaptoamine (2 drops) and two Gasified sulfoxide (2 〇 ml, 27 mM). The solution was stirred at ambient temperature for a few hours and concentrated in vacuo to give 2-(carbomethyl)- 3,5-difluoropyridine hydrochloride (2 31 g, recommended) as brown oil. Rf = 0.71 (EtOAc / hexane, 1/1). Preparation 86 2-(A gas-based fluorenyl)_4-fluoroyl p-bitate hydrochloride synthesis of 4-aminopyridylcarboxylic acid methyl vinegar (〇·5 gram, 32 〇 millimolar) in tetrahydrofuran In a solution (20 ml), at _78 χ: τ, lithium aluminum hydride (〇15 g, 4.00 mmol) was slowly added. The solution was stirred for 2 hours and water (ml) was added. The reaction mixture was allowed to warm to ambient temperature, dried over magnesium sulfate, MgSO4, &lt;RTI ID=0.0&gt;&gt;&gt;&gt;&gt; For light η color oil. To the solution of this oil in dioxane (1 mL) was added sulfite (1.0 mL, 13 mmol) and the solution was stirred at ambient temperature for 16 hours. The solution was concentrated in vacuo to give EtOAc (EtOAc: EtOAc (EtOAc) -8.47 (m,1Η), 7.04-6.90 (m,2Η), 4.74 (s,2Η). Preparation 87 5-Bromo-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl H-pyridin-2-ylindenyl)-1,3 Synthesis of dihydro-2H-4 ace-2-one A. 5·Bromo·1·(Ρ比pyridine.2·ylmethyl)·1Η_吲哚_2,3_dione synthesis in 5 - bromo hydrazine (ιαο克, 44.4 mmol) in a solution of anhydrous hydrazine, hydrazine _: methyl decylamine (100 ml), in hydrazine. Under the arm, slowly add sodium hydride (60% w/w dispersion in mineral oil, 3.90 g, 97.7 mmol). Stir the solution for 30 minutes and add 2-(bromo-based) phenol to bite. Hydrobromide salt (η 2 g, 44 4 mmol). The solution was stirred at ambient temperature for 16 hours and poured into ice water (13 liters) and vigorously stirred to cause sediment deposition. The solid was collected by filtration to give 5-bromo-l-O.sup.~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Nmr (300 mhz, CDCl3) δ 8 55·8 5〇(m,m), 7.72-7.56 (m, 1H), 7.34-7.28 (m, 1H), 7.25-7.18 (m, 1H), 6.93-6.88 (m, 1H), 5.03-4.99 (m, 2H). Β· 5-Bromo- 3·hydroxy-3-(7-hydroxy·2,3-dihydro·1,4·benzodioxene-6—yl)·1-(ρ ratio bite·2_ Synthesis of 1,3-diaza-2Η-Ή丨嗓-2-嗣 in 2,3-dihydrobenzo[b][l,4]dioxolene-6-ol (2 • 55 g, 16.8 mmoles) in a solution of anhydrous dichloromethane (1 mL) in hydrazine. Addition of 〇 143924-sp-20091127-1 -295- 201020257 propyl magnesium hydride (2M solution in tetrahydrofuran, 10.0 ml, 19 9 mmol). The solution was stirred at 0 °C for 20 min and 5-bromo-1 -(pyridin-2-ylmethyl)-1 hydrazino-p-indole-2,3-dione (4.85 g, 15.3 mmol) was added. The reaction mixture was stirred at ambient temperature for 16 hours, a saturated aqueous solution of EtOAc (25 mL) was then taken and the mixture was concentrated in vacuo. The residue was triturated with ethyl acetate (25 mL) and the solid was collected by filtration to give 5-bromo <RTI ID=0.0>3 </ </ </ </ Oxide terpenes) (Pyridine 2 -ylmethyldihydro-2H-+, -2-) (7.26 g '98%), as a beige solid: 1 η NMR (3 〇〇 MHz, DMSO -d6) δ 9.20 (s, 1Η), 8.71 (d, J = 4.9 Hz, 1H), 8.06 (dd, J = 7.80 ❹ Hz, 1H), 7.63-7.55 (m, 2H), 7.52 (d, J = 8.0 Hz, 1H), 7.35 (dd, J = 8.3, 2.0

Hz, 1H), 7.20 (s, 1H), 6.99 (d, J = 2.0 Hz, 1H), 6.82 (d, J = 8.3 Hz, 1H), 6.16 (s, 2H), 5.09 (ABq, 2H), 4.20-4.10 (m, 4H) 〇C· 5-enyl-3-(7-hydroxy-2,3·dihydro-l,4-benzodioxanthene_6_yl^7-pyridinium· Synthesis of 2-ylmethyl)-1,3-dihydro-2H-W哚-2·one from 5-bromo-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1, 4-benzodioxolysene _6_yl)-1-0 butyl-2-ylindenyl)-i,3-dihydro-2H-M丨哚-2-one (3.60 g, 8.10 mmol) In the suspension in diethyl decane (1 liter ml), in hydrazine. Under the armpit, add trisodium fluoroacetic acid (40 ml). The solution was allowed to warm to ambient temperature over 2 hours and stirred for an additional 4 hours. The reaction mixture was concentrated in vacuo, and a saturated aqueous solution of sodium hydrogencarbonate and ethyl acetate were added to the residue to cause sedimentation. The solid was collected by filtration and washed successively with diethyl ether and hexane to give 5-bromo-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxene _6•yl) Small (pyridine-2-ylguanidino H,3-dihydro-2H-indol-2-one (4.03 g, 1%) as a pale yellow solid: NMR (300 MHz, DMSO-d6) δ 8.59 -8.55 (m,1H), 7.90-7.80 (m, -296- 143924-sp-20091127-l (S) 201020257 1H), 7.44-7.37 (m, 1H), 7.34-7.27 (m, 1H), 7.07 (s, 1H), 6.82-6.68 (m, 2H), 6.27 (s, 1H), 5.17-4.93 (m, 2H), 4.84 (s, 1H), 4.23-4.06 (m, 4H). MS (ES+ m/z 452.9 (M + 1), 454.9 (M + 1). Preparation 88 5-'/Sandyl-1-(monomethyl)-3-(7-yl-phenyl-2,3-dihydro) Synthesis of 1,4-1,4-benzodioxanthene _6_yl-gas cough-2-oxime A. 5-bromo-1-(diphenylmethyl)-1H-indole-2,3-dione The synthesis was carried out according to the procedure as described in Preparation 26A, and the insignificant changes were made, © using 2_bromo 4哚醌 to replace 2,3-dihydro-6H-[1,4]dioxene. 2,3-fH 嗓-7,8-dione' and replacing 2_(bromomethyl)_5-(trifluoromethyl)furan with bromodiphenylmethane to obtain 5-bromo-l-(diphenylmethyl) )_1H_吲哚_2,3_two (76%): 1H NMR (300 MHz, CDC13) 3 7.74-7.67 (m, 1H), 7.46-7.20 (m, 11H), 6.96 (s, 1H), 6.37 (d, J = 8.5 Hz, 1H) B. 5-Molyl-H diphenylhydrazinyl)-3•hydroxy·3_(7-hydroxy-2,3_dihydrogen such as benzodioxene _6·yl)·1,3. Dihydrogen ❿ Η * * * * * ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ ❿ 3 diketone replacement 5 _ _ 7-7-pyridin-2-yl fluorenyl)-1 Η-吲哚-2,3-dione, to obtain 5-bromo small (diphenyl fluorenyl) _3 hydroxy-3- (7-Carbyl-2,3-dihydro-1,4- benzodioxanthene, dimethyl-dihydro-211-nonan-2-one (64%)' is a pale yellow solid: Ms (ES+ ) _ 525.9 (Μ _ 17), 527.9 (Μ -17). C. S-glycine-1-(diphenylmethyl)-3·(7-hydroxy-2,3-dihydrobenzodioxanthene-6-yl)-1,3-dihydro-2Η - 啕嗓.2. Residual synthesis according to the procedure as described in Preparation 82C, and the implementation of insignificant changes, 143924-sp-20091127-1 • 297· 201020257 using 5-bromo-1-(diphenylmethyl) Each hydroxyl group _3_(7 hydroxy 2 3 dihydro-14 benzodioxanthene-6-yl)-1,3-one enthalpy-2-yl substitution; [_(diphenylmethyl) _4_Fluoro-3-hydroxy-3-(7-radio-2,3-dihydro-l,4-benzodioxanthene-6-yl from ^dihydro-2H-indole-2 a ketone to obtain 5-bromo small (diphenylmethyl) each (7-hydroxy-2,3 dihydro-1,4-benzodioxanthene-6-yl)-1,3-dihydrogen -2H-Indol-2-one (85%) as a colorless solid: MS (ESI) m/z 527.8 (M + 1), 529.8 (M + 1). Synthesis of (5-fluoro-7-hydroxy-2,3-dihydrobenzodioxene-6-yl)-1,3-dihydro-2H-indol-2-one ▲•7- Synthesis of bromo-5-fluoro-2,3-dihydrobenzo[1)][1,4]dioxanthene 5-fluoro-2,3-dihydroindol[b][ l,4]dioxanthene (1 54 g, 1 〇〇 mmol) and 1-bromotetrahydropyrrole-2,5-di (1.8 g, 1〇 mmol) and the solution was heated in methanol (2〇 mL) at reflux for 0.5 hours, allowed to cool to ambient temperature, and concentrated in vacuo. The residue was dissolved in dichloromethane (9 mL) and washed water (50 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate ethyl acetate in 0% to 30% gradients of hexanes to afford 7 bromo-5 fluoro bis- 2,3-dihydrobenzo[b][ 1,4] Dioxetene (2.04 g, 87%), m.m. Synthesis of Β·8·fluoro- 2,3-dihydrobenzo[1)][1,4]dioxanthene·6 alcohol in 7-formyl-5-fluoro-2,3-di Hydrogen benzo[b][1,4]dioxanthene (i5 j, 64.8 mmol) in tetrahydrotetramine (160 ml), under _78, plus n-butyl A 1.6 M solution of lithium lithium in hexane (45 mL, 73 mmol). The reaction mixture was stirred at -78 °C for 15 minutes and tridecyl borate (85 143924-sp-20091127-1 -298-201020257 g &apos; 82 mM) was added. The reaction mixture was allowed to warm to ambient temperature, stirred for 48 hours and cooled to 5 °C. A 35% w/w aqueous hydrogen peroxide solution (i 26 mL, 129.6 mmol) was added and the mixture was warmed to ambient temperature and stirred for 3 h. The reaction mixture was diluted with EtOAc (EtOAc) (EtOAc)EtOAc. Purify the residue by chromatography, vinegar

Ethyl acetate was dissolved in a gradient of 0% to 70% in hexane to give 8-fluoro-23-dihydrobenzo[b][l,4]dioxolene-6-ol (6.5 g, 59%), as a colorless solid: MS (ES+) m/z 153.0 (M -17). C·1·(diphenylmethyl)-3_(s_fluoroyl-7hydroxyl-2,3-dihydro-M_benzodioxanthene-6-yl)-3-hydroxy·1,3 Synthesis of di-argon-2H-indol-2-one in a 100 ml round bottom flask filled with 8-1 base 2,3-dihydrobenzo[b][i 4]dioxene terpenene-6 - Alcohol (6.4 g, 37 mmol) with tetrahydrofuran (6 liters). At 5 C, a 2 m solution of isopropylmagnesium chloride in tetrahydro odor (2 〇. 〇 ml '40.0 mmol) was added and the reaction mixture was stirred for 15 minutes. The reaction mixture was concentrated in vacuo and EtOAc (EtOAc &lt ) A solution in a second gas (6 ml). The reaction mixture was heated under reflux for 5 hours, allowed to cool to <RTI ID=0.0> A saturated aqueous solution of acetic acid (30 ml) was added, and the liquid phase was separated. The organic phase was dehydrated and dried over magnesium sulfate, filtered and concentrated in vacuo. EtOAc EtOAc EtOAc EtOAc Benzyl-2,3-dihydro-1,4-benzodioxanthene-6-yl)-3-hydroxy-1,3-dihydro-2H-choline-2-one (10.8 g, 64%), as an off-white solid: MS (ES+) m/z 506.0 (M + 23). 143924^sp-20091127-l -299- 201020257 D. 1·(Diphenylmethyl)-3-(5-fluoro-7-hydroxy-2,3-dihydro·Μ·benzodioxanthene Synthesis of -6-yl)-1,3-dihydrobromo-2_ Ming according to the procedure as described in Preparation 82C, and irrelevant changes were made using 1-(diphenylmethyl)-3-(5) -fluoroyl-7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-3-yl-l-1,3-dihydro-2Η-choline-2 -keto-substituted 丨_(di-p-methyl)_4•-yl-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene) H,3_ : Hydrogen-2H-indol-2-one, obtaining H-diphenylmethyl)_3_(5.fluoroyl-7-hydroxy-2,3-dihydro-1,4-benzodioxene olefin-6 · Dihydrogen 2 Η 吲哚 吲哚 ketone (85%), as an off-white solid: MS (ES+) m/z 467.9 ( Μ + 1). Preparation of 90 Ηdiphenylmethyl)-3-(6-hydroxyl Synthesis of -3,4-dihydro-2H-nonene-7-yl H,3-dihydro-2H-indol-2-one in a 500 ml round bottom flask filled with 咣6-alcohol (92 g , 61 mM) and tetrahydrofuran (120 ml). Add 2M solution of isopropylmagnesium chloride in tetrahydrofuran (32. 5 ml, 65'0 mmol) at 5 °C. Reaction mix Stir for 15 minutes and concentrate in vacuo. Underneath, add di-methane (18 mL), followed by H-diphenylmethylhydrazine, 2,2dione (18.8 g, 60.0 mmol) A solution of dioxane (18 mL). The reaction mixture was warmed to ambient temperature and stirred for 24 hr. A saturated aqueous solution of ammonium chloride (7 mL) was added and the mixture was concentrated in vacuo. Preparation of the product in decyl alcohol/water (1/100, 200 ml) to obtain i (diphenylmethyl hydrazino- 3 ♦ benzyl-3,4-dihydro-2 fluorene-nonene) _u· Dihydro 2 Η•吲哚_2•. Η Η 曱 ) ))-3-hydroxy-3-(6-hydroxy-3,4-dihydro 2 Η 咣 咣 _ _ _ , , , , Dihydro-2H-indol-2-one, triethyl decane (23.2 g, 2 〇〇 mmol), trifluoro vinegar 143924-SP-20091127-1 -300- 201020257 acid (50.0 g, 438 mmol) The mixture was stirred at ambient temperature for 20 hours and concentrated in vacuo. The residue was crystallised from EtOAc (EtOAc) (6-hydroxy-3,4 dihydro-benzene-7-yl)-1,3-di -2Η- indol-2-one (24.3 g, 90%) as an off-white solid: MS (ES +) m / z 448.0 (Μ + 1). Preparation 91 Synthesis of 1-(diphenylmethyl)-3-(5-hydroxy-1-benzothiophene-6-yl)-1,3-dihydro-2HH2-one β Α· 1-(diphenylfluorenyl) Synthesis of 3-hydroxy.3-(5-hydroxy-l-benzopyrene-6-diazepine-2H-W哚-2-one to benzo[b]thiophene-5-ol (1.39 g, A solution of isopropylmagnesium hydride in tetrahydrofuran in 2M (5 mL, 1 mL of millimolar) was added to a solution of THF (5 mL) in tetrahydrofuran (5 mL). The reaction mixture was stirred at 5 ° C for 15 min and concentrated in vacuo. EtOAc &lt 2.5 g, 8 〇 ❹ ❹. The reaction mixture was heated under reflux for 3 hours, allowed to cool to the temperature of the ring, and stirred for 48 hours. Add saturated aqueous chloride (1 mL) and separate The organic phase is dehydrated and dried with magnesium sulfate, filtered, and dried in vacuo. The residue is purified by column chromatography and eluted with ethyl acetate in a 0% to 20% gradient of the gas. And μ(diphenylmethyl)_3_carbyl-3-(5-pyridyl-1-benzocyano-6 -基)_ι,3_ Dihydro-p-butan-2-one (2.2 g, 59%) ' is an off-white solid: MS (ES+) m/z 486.0 (M + 23). Β· 1-(diphenylmethyl) Synthesis of -3-(5-hydroxy-1-benzopyrene-6.yl)4,3-dihydro-2H• Qiao丨哚-2-嗣 143924-SP-20091127-1 -301 - 201020257 Procedure described in 82C, and insignificant changes, using 1-(diphenylfluorenyl)-3-yl-based 3-(5-hydroxybenzobenzophenanyl)13-dihydro-2H-(f)pyrene -2-oxime substituted 1-(diphenylfluorenyl) 4 fluoro-3-3 hydroxy·3 (7 hydroxy 2,3_dihydro-1,4-benzoxa-Oxaloene-6 hydrazine) dihydrogen · 2Η•啕哚_2_ketone, obtained Η-benzyl)-3-(5-3⁄4 base, ^ stupid and 喳6 _6 base) 13 dihydro 2 Η吲哚-2_ 嗣 (94%) ' It is an off-white solid: Ms (ES+) m/z 448 l (M + i). Preparation 92 Ηdiphenylhydrazinyl)-3-(5-hydroxy-2,u-benzo, oxadiazole) 13 dihydrogen Synthesis of _2H啕哚-2-ketone A. 1-(Diphenylfluorenyl)-3-hydroxy.3.(5.Hydroxybenzoxadiazole_4_yl H,3-dihydro-2H·» »5丨嗓·2· Ketone synthesis According to the procedure described in Preparation 2Α, and the implementation of irrelevant changes, use 2,1,3 stupid number one _5-alcohol replacement of 3 bromophenol, and replacement of 1-((5-(trifluoromethyl)furan-2-yl)methyl) with hydrazine (diphenylmethyl)-1H-indole-2,3-dione Hydroquinone-2,3-dione, 丨((diphenylmethyl)-winter hydroxy (5-hydroxy-2丄3 benzoxazol-4-yl)-1,3-dihydro-2H -Indol-2-one (71%) 'Colorless solid: MS (ES+) m/z 472.0 (Μ + 23). Diazol-4·yl)-1,3-dihydro-2Η-Β·1·(diphenylfluorenyl)-3-(5-radio- 2,1,3-benzoindole·2_ The synthesis of hydrazine will be 1-(diphenylmethyl)-3-carbyl (5-hydroxy-2,u-benzoxadiazole_4yl)-indole, 3 dihydro-2H-indole-2- A mixture of the ketone (21.8 g, 48.5 mmol), triethyldecane (5 mL) and trifluoroacetic acid (1 mL) was stirred at ambient temperature for 16 hours and then heated to 45t: for 1.5 hours. The mixture was allowed to cool to ambient temperature and concentrated in vacuo. The residue was crystalljjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj , 1,3-benzo-p-di-β-sodium _4·yl)-i,3-dihydro-2Η-indol-2-one (10.94 g, 52%), as colorless solid: 1H NMR (300 MHz, CDC13) (5 10.90-10.00 (br s, 1H), 7.61-7.31 (m, 10H), 7.18 (s, 1H), 7.06-6.89 (m, 4H), 6.55 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 9.6 Hz, 1H), 5.57 (s, 1H); MS (ES+) m/z 456.0 (M +23). Preparation 93 3-(7-chloro-6-hydroxy- 2,3-dihydro-1,4-benzodioxanthene 浠_5_yl)_i_(diphenylmethyl)_1,3--disorder p-嗣Synthesis of A. 7-Alkyl-2,3·dihydrobenzo[b][l,4]dioxanthene-6-alcohol synthesis at ambient temperature '6-hydroxy-1,4- Benzodioxanthin (1.52 g, 1 mmol) in a solution of N,N-dimercaptocaramine (1 mL), N-chloropyranimide (1.33 g) , 10 mM. The solution was stirred at ambient temperature for 16 hours and concentrated in vacuo. The residue was purified by column chromatography eluting with 15% to 30% of ethyl acetate in hexane. Dissolved to give 7-glycol-2,3-dihydrobenzo[b][i,4]dioxene _6-alcohol (1.79 g, 96%) as a colorless solid: 1H NMR (300 MHz, CDC13) &lt;5 8.02 (s, 1H), 6.83 (s, 1H), 6.56 (s, 1H), 4.27-4.16 (m, 4H). Β· 3-(7-gas-based-6 -hydroxy-2,3·dihydro-1,4-benzodioxanthene-5-yl)-1-(diphenylindenyl)-3-trans-yl-1,3-dihydro·2Η· The synthesis of ketone-2 ketone was carried out according to the procedure described in Preparation 2, and the inconsequential changes were made using 7-chloro-2,3-dihydrobenzo[b][i,4]dioxene. Terpene-6-ol replaces 3-bromopan and uses 1-(diphenylfluorenyl)_1H-吲哚_2, 3_dione replacement of 1-((5-(trifluoromethyl)phosphonium 11-N-2-yl)methyl)indoline-2,3-dione to give 3_(7-chloro group_6_ Hydroxy-2,3-dihydro-l,4-benzodioxanthene _5-yl) small (diphenyl fluorenyl) 3 hydroxy n 143924-sp-20091127-1 -303· 201020257 Dihydro-2H -W 哚-2-one (18%) as a colorless solid: MS (ES+) _ 522 1 (M + 23), 524.1 (M+23). C·3·(7-Gas-6-hydroxy-2,3-dihydro·1,4·benzodioxene-5·yl) small (diphenylfluorenyl)·1,3-di The synthesis of hydrogen-2Η·+果-2-嗣 was carried out according to the procedure described in Preparation 2Β, and the irrelevant change was carried out using 3-(7-aero-6-hydroxy-2,3-dihydro, ι, 4-benzodioxanthene _5-yl) small (diphenylmethyl)-3-yl-1,3-di-argon-2-indole-2-one substituted 3-(4-bromo group -2-hydroxyphenyl)-3-carbyl-1-{[5-(trifluoromethyl) methoxymethyl]methyl b 1&gt;3_dihydro-2-indol-2-one, obtained 3 -(7-alkyl-6-hydroxy-2,3-dihydro-1,4-benzodioxanthene-5, ruthenium) small (one fluorenyl hydrazine, 3-dihydro-2 fluorene- Indole-2-one (74%) as a colorless solid: !H NMR (300 MHz, CDC13) ά 7.44-7.27 (m, 10 Η), 7.08-6.78 (m, 4H), 6.49-6.42 (m, 1H ), 5.76 (s, 0.5H), 5.30 (s, 0.5H), 5.27 (s, 0.5H), 5.03 (s, 0.5H), 4.39-4.25 (m, 2H), 4.06-3.90 (m, 1H) ), 3.75-3.50 (m, 1H); MS (ES+) m/z 484.3 (M + 1), 486.3 (M + 1). Preparation 94 3-(4,5-difluoro-2-hydroxyphenyl) Synthesis of -1-(diphenylfluorenyl) 4,3-dihydro-2H_^哚_2-one A· 3-(4,5-difluoro-2-hydroxyphenyl) small (diphenyl) Synthesis of hydrazinyl hydrazine θ 嗣 嗣 嗣 嗣 嗣 嗣 嗣 嗣 嗣 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成Phenol, and the replacement of 1-((5-(trifluoromethyl)fluoren-2-yl)indenyl) indoline with ι_(diphenylmethyl)_1Η_啕哚_2,3_dione 2,3_dione, 3-(4,5-difluoro-2-hydroxyphenyl)small (diphenylmethyl)_3_carbyl-1,3-dihydro-2Η-吲哚-2- Ketone (61%) ' is a colorless solid: 1hnmr (300MHz, CDC13) &lt;5 9.23(br s, 1H), 7.47-7.44 (m, 1H), 7.35-7.21 (m, 9H), 7.18-7.11 (m , 2H), 6.90 (s, 1H), 143924-sp-20091127-l • 304_ 201020257 6.83 (dd, J = 11.2, 6.9 Hz, 1H), 6.67 (dd, J = 11.2, 8.7 Hz, 1H), 6.56 -6.51 (m, 1H), 4.13 (br s, 1H) ; MS (ES+) m/z 426.2 (M -17). B. Synthesis of 3-(4,5-difluoro-2·phenyl)-1.(diphenylmethyl)_i,3_dihydro-2jj•吲嗓_2-one according to Preparation 2B The procedure described, and irrelevant changes, using 3-(4,5-difluoro-2-hydroxyphenyl)succinyl(diphenylmethyl)_3_ylamino-2H_^indol-2-one -(4-bromo-2-hydroxyphenyl)·3-hydroxytrifluoromethyl)methane-2-yl]methyl}-1,3-hydrogen-2Η-Ϊ1丨嗓丨嗓-2-明, 3-(4,5-diI -2-benzoyl)-small (monobenzylH,3-dihydroanthracene-*1?b--2-) (56%), obtained as off-white Solid: 1H NMR (300 MHz, CDC13) δ 9.27 (br s, 1H), 7.37-7.12 (m, 12H), 6.94 (s, 1H), 6.87 (dd, J = 11.3, 7.1 Hz, 1H), 6.76 (dd, J = 11.2, 8.9 Hz, 1H), 6.58-6.56 (m, 1H), 5.12 (s, 1H); MS (ES+) m/z 428.2 (M + 1). Preparation 95 1-(diphenyl) Synthesis of fluorenyl)-3-(3-carbyl-5,6,7,8-tetrahydroindol-2-yl)-1,3-dihydro-2H-indol-2-one Synthesis of -(diphenylmethyl)-trans-3·0-hydroxy-5,6,7,8-tetrahydronaphthalene·2-yl-w,3·dihydro-p-butyl-2-pyrene as described in Preparation 2Α The procedure, and the implementation of irrelevant changes, using 5,6,7,8-tetrahydro-2-naphthalene 3-indifferent, and the replacement of 1-((5-(trifluoromethyl)pyran-2-yl)indenyl) dihydrogen with ι_(diphenylfluorenyl) 4Η-吲哚-2,3-dione Indole-2,3-dione, 1-(diphenylhydrazinyl)-3-yl-3-(3-carbyl-5,6,7,8-tetrahydroindol-2-ylindole, 3-Dihydro-2Η-indol-2-one (76%) 'Colorless solid: iH NMR (300 MHz, CDC13) δ 8.73 (s, 1H), 7.52-7.49 (m, 1H), 7.32-7.28 (m, 10H), 7.09 (dd, J = 5.6, 3.2 Hz, 2H), 6.95 (s, 1H), 6.75 (s, 1H), 6.51-6.48 (m, 2H), 4.31 143924-SD-20091127- 1 • 305- 201020257 (s, 1H), 2.70 (br s, 2H), 2.52 (br s, 2H), 1.72 (br s, 4H) ; MS (ES+) m/z 444.1 (M-17). Synthesis of 8.1-(monophenylmethyl)_3-(3_hydroxy-5,6,7,8-tetrahydronaphthalene-2-yl)_1,3-dihydro-211_啕哚-2-嗣Injuring the procedure described in 2B' and performing an insignificant change, using 1-(diphenylhydrazinyl)-3-hydroxy-3_(3_hydroxy-5,6,7,8 tetrahydroindole-2-yl H,3 -Dihydro-2H-indol-2-one replaces 3-(4-bromohydroxyphenyl)hydroxy-1-([5-(trifluoromethyl))-2-yl]methyl}- 1,3_Dihydro-2H-indol-2-one, 1-(diphenylmethyl)-3-(3-carbyl-5,6,7,8-tetrahydronaphthalenehydrogen-2H , 哚_2_ketone (71%), as a colorless solid. iHNMR (300MHz, CDC13) 5 8.41 (s,1H),7.33-7.29 (m, 9H), 7.24-7.22 (m, 2H), 7.10-7.07 (m, 2H)S 6.98 (s, 1H), 6.80 (s, 1H), 6.64 (s, 1H), 6.56-6.53 (m, 1H), 5.13 (s, 1H), 2.73 (br s, 2H) , 2.60-2.56 (m, 2H), 1.74 (br s, 4H); MS (ES+) m/z 446.0 (M + 1). Preparation 96 3-(7-hydroxy-2,3-dihydro-1, 4-benzodioxantemene_6_yl)_4,5-dimethoxy small {[5-(difluoromethyl)anthracene]Nan-2-yl]methyl}_1,3_dihydrogen Synthesis of -2H-indol-2-one 4· 4,5·dimethoxy-1_{[5-(trifluoromethyl)pyran-2-yl]methyl b 1H_啕哚_2, 3_ diketone The procedure described in Preparation 26A was carried out, and irrelevant changes were made, and 2,3-dihydro-6H-[1] was replaced with 4,5-dimethoxyindoline 2,3-dione. , 4] Dioxetidene [2,3-fH哚-7,8-dione, 4,5-dimethoxy-1-([5-(trifluoromethyl)hydrazine-2] -yl] fluorenyl}-1Η-吲p-toly, 2,3-dione (51%) as a red solid: NMR (300 MHz, DMSO-d6) δ 7.22 (d, J = 8.5 Hz, 1H), 7.17-7.12 (m, 1H), 6.77-6.70 (m, 2H), 4.94 (s, 2H), 3.96 (s, 3H), 3.72 (s, 3H). 143924-sp-20091127-1 -306· 201020257 B. 3-Hydroxy-3-(7-hydroxy·2,3-dihydrodecene benzodioxanthene-6_yl)_4, dimethoxy-1·{[5-(trifluoromethyl) Synthesis of thiol-2-yl]methyl}-1,3-dihydro-2-indol-2-one. According to the procedure described in Preparation 2, and irrelevant changes are used, 2 is used. 3_Dihydrobenzo[1,4]dioxolysine-6-yield to replace 3-bromophenol, and 4,5-dimethoxy-indole_{[5-(trifluorofyl)furan _22-methyl-2-(3,2-dione)-substituted 1-((5-(difluoroindolyl)pyran-2-yl)methyl)indoline_2,3-dione , 3-hydroxy-3-(7-hydroxy-2) ,3-dihydro 4,4-benzodioxene terpene _6_yl)_4,5-di-methoxycarbonyl trifluoromethyl)furan-2-yl]methyl}-l,3-di Hydrogen-2Η-吲哚-2-嗣 (67%) 'is a colorless solid: 1Η cutlery (3〇〇MHz, CDC13) occupies 8 59 &amp; Qiu, 6.88 (d, J = 8.4 Hz, 1H), 6.71 -6.65 (m, 1H), 6.61 (d, J = 8.4 Hz, 1H), 6.54 (s, 1H), 6.33-6.25 (m, 2H), 4.89-4.71 (m, 2H), 4.25-4.02 (m , 4H), 3.99 (s, 1H), 3.83 (s, 6H, C. 3-(7-hydroxy·2,3·dihydro·1,4-benzodioxene. Bu) _4, 5_Dimethoxy 1_{[5·(Tri-I yl) coughing · 2 yl] fluorenyl} 4,3_ dihydro. 2 η _ ρ 5 卜 嗣 -2 嗣 synthesis according to the procedure as described in Preparation 4C And the insignificant change was carried out using 3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-ylindole, 5-methoxy- 1-{[5-(di-Imethyl)pyran-2-yl]methyldi, 3_dihydro, 2η_ρ5| ρ-butan-2-one-substituted 4-yl-1-(phenylenemethyl) )_3_ via the base _3_(6_transyl 2,3_dihydrobenzophthalazin-5-yl)-1,3-dihydro-2Η-indol-2-one' obtained 3-( 7-Hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-4,5-dimethoxy-oxime _{[5-(Trifluoromethyl)pyran-2-yl]methylindole '3-dihydro-2Η-indol-2-one (83%) ' is a colorless solid: ihnmr (300 MHz, CDC13 ) 6.86 (d, J = 8.5 Hz, 1H), 6.71-6.67 (m, 1H), 6.66-6.60 143924-sp-20091127-1 -307- 201020257 (m, 2H), 6.32-6.25 (m, 2H ), 5.11 (s, 1H), 4.94-4.76 (m, 2H), 4.23-4.07 (m, 5H), 3.84 (s, 3H), 3.74 (s, 3H). Preparation 97 3-(7-Hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-4,7-dimethoxy-l-[2-(2- Synthesis of decyloxyethoxy)ethyl]-i,3-dihydro-2H-indol-2-one A. 3-hydroxy-3-(7-hydroxy-2,3-dihydro-1, 4·benzodioxanthene-6·yl)-4,7-dimethoxy-1-[2-(2-methoxyethoxy)ethyl]_ι,3·二氲.2H Synthesis of -W哚-2-yl in 4,7-dimethoxy-1Η-indole-2,3-dione (1.8 g, 8.7 mmol) in anhydrous ❹ Ν, Ν-dimethyl A solution of decylamine (2 mM) and anhydrous tetrahydrofuran (12 mM) was added at room temperature (11. 4 g, 35 〇 millimolar). The mixture was stirred at ambient temperature for 30 minutes and a portion of bromo-2-(2-methoxyethoxy)-hexane (2.35 mL, 17.4 mmol). The mixture was stirred at ambient temperature for 16 hours' concentrated in vacuo to a small volume and poured into ice water (300 mL). The mixture was extracted with ethyl acetate and the combined organic extracts were filtered thru a pad. The filtrate was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Preparation of the residue in hexane, 10 gave 4,7-dimethoxy-indole 2-(2-methoxyethoxy)ethyl]-1Η-呻哚-2,3-di-(2.2 g '82%). Displace the 3-bromophenol with 2,3-dihydrobenzopyrene]dioxanthene-6-ol and use 4,7-di according to the procedure described in Preparation 2, and subject to irrelevant changes Dissociation of 1-((5-(trifluoromethyl)pyran-2-yl)indolyl) with a small amount of decyloxy[2_(2-methoxyethoxy)ethyl]_1Η吲哚_2 3dione Dihydroindole 2,3_dione, obtaining 3-cysyl-3-(7-transyl-2,3-dihydro-1,4-benzodioxanthene-6-yl)_4, 7_Dimethoxy 143924-SP-20091127-1 201020257 Base-l-[2-(2-decyloxyethoxy)ethyl H,3_:hydrogen 2Hm嗣 (53%): MS (ES+) m /z 443.9 (Μ - 17) ο Β. 3-(7-Hydroxy-2,3.dihydro.;!,4·benzodioxene) _4,7-dimethoxy-1- [2. (2-methoxyethoxy)ethyl hydrazine, 3. Dihydro _211_ 丨哚 丨哚 _2 ketone synthesis according to the procedure as described in Preparation 4C, and the implementation of irrelevant changes, Using 3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4- benzodioxanyl-6) 4,7-dimethoxy-l-[2-(2- Methoxyethoxy)ethylh,3 dihydro-2H_throquinone-2-keto-substituted 4-carbyl-1-(diphenylmethyl)_3_hydroxy_3_(6-hydroxy-2 3_2 Hydrogen small benzofuran® _5_yl)_1,3_ Dihydro-2H_吲哚_2_ketone' obtained 3-(7-transyl 2,3-dihydro-I,4-benzodioxanthene-6-yl)-4,7-di Methoxy small [2_(2-methoxyethoxy)ethyl]-1,3-dihydro-2H-indol-2-one (89%) as a yellow solid: MS (ES+) (Μ + 1). Preparation 98 8-(7-Hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)_6_[2_(2-methoxyethoxy)ethyl]-2 Synthesis of 3,6,8-tetrahydro-7Η41,4]dioxanthene[2,3-f]indole-7-one Α·6-[2·(2-methoxyethoxy Synthesis of ethyl]ethyl]_2,3-dihydro-6H-[1,4]dioxolynene [2,3-fH哚-7,8-dione according to the procedure described in Preparation 97A And the implementation of irrelevant changes, using 2,3-dihydro-6H-[1,4]dioxolene and [2,3-fl 啕哚-7,8-dione (Lackey and 51611 ^ mad (^1, do "Jielie &amp; 1993: 993-997" to replace 4,7-dimethoxy-111-indole-2,3-dione to obtain 6-[2-(2-decyloxy) Ethoxy)ethyl]_2,3-dihydro-6H-[1,4]dioxolynene[2,3-f]indole-7,8-dione (82%) : 1H NMR (300 MHz, DMSO-d6) &lt;5 7.05 (s, 1H), 6.78 (s, 1H), 4.37-4.32 (m, 2H), 4.24-4.17 (m, 143924-sp-20091127-l -309- 201020257 2H), 3.74 (t, J = 5.5 Hz, 2H), 3.56 (t, J = 5.5 Hz, 2H), 3.50-3.44 (m, 2H), 3.36-3.30 (m, 2H), 3.14 (s, 3H) Β· 8-hydroxy-8-(7-hydroxy-2,3·dihydroindolyl, 4-benzodioxanthene.6-yl)_6·[2·(2-decyloxy Synthesis of ethoxy)ethyl]-2,3,6,8-tetrahydro-7 Η-[1,4]dioxo-aree[2,3-f]»5丨嗓-7-嗣 according to Prepare the procedure described in 2A and perform irrelevant changes by replacing 2-3-bromophenol with 2,3-dihydrobenzo[b][l,4]dioxanthene alcohol, and using 6-[ 2-(2-methoxyethoxy)ethyl]_2,3·dihydrodioxolysine[2,3-fH嗓-7,8-dione substituted 1_((5_(trifluoromethyl)吱 _2 _2 _ _2 _2 _2 _2 _2 ) ) ) ) ) ) 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 ' 嗓 嗓 嗓 嗓 ' ' ' 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓 嗓Oxadecene-6-yl)-6-[2-(2-methoxyethoxy)ethyl]_2,3,68-tetrahydro- melon-like]dioxanthene [2,3 -f]吲哚-7-ketone (19%): MS (ES+) m/z 441.9 (M -17). C. 8-(7- mercapto-2,3-dihydro-1,4 benzo Dioxerecan·6_yl)·6_[2-(2-methoxyethoxy)ethyl]-2,3,6,8-tetrahydro-7Η-[1,4]dioxene Synthesis of octa[2,3-f]吲嗓7- Ming according to the procedure as described in Preparation 4C, and performing an insignificant change, using 8-hydroxy-8-(7-hydroxy-2,3- Dihydro-1,4-benzodioxanthene _6_yl)_6_ ® [2-(2-decyloxyethoxy)ethyl]_2,3,6,8 -tetrahydro-7H-[1,4]dioxantholine and [2,3-f]吲哚-7--substitution of 4-chloro-i-(diphenylmethyl)-hydroxyl groups (6-hydroxyl groups) _2,3_Dihydro-1-benzofuran-5-yl)-1,3-dihydro-2H-indol-2-one, obtaining 8-(7-hydroxy-2,3-dihydro-1 , 4-benzodioxanthene _6_yl)_6_[2_(2 methoxyethoxy)ethyl]-2,3,6'8-tetrahydro-7H-[1,4] Oxygen-ene-ene [2,3-handle- 7-ketone (54%), as a pale yellow solid · MS (ES+) m/z 443.9 (M + 1). 143924-SP-20091127-1 -310- 201020257 Preparation 99 8-(7-Pyloryl-2,3-dihydro-1,4-benzoxanoxaxene_6_yl)·6_(4_曱Oxy-aryl)-6,8-dihydro-7Η-[1,3&gt; plug" sit and [5,4«嗓-7-class synthesis A. 6-(4-methoxybenzyl)- 6Η_[1,3}* 塞 sn sn [5,4_e&gt;5 noisy-7,8_diming synthesis in 1,3-benzo[d]*»zepa-6-amine (1〇.〇克, 66.6 millimolar) and a mixture of 4-fennel (8.5 ml '70 mmol) in 1'2-dioxaethane (350 ml) at ambient temperature with diethyl hydrazine Sodium (28.2 g, 133.0 mmol). The mixture was stirred at ambient temperature for 16 hours and an aqueous solution of hydrogen in sodium hydroxide was added. The organic layer was concentrated in a vacuum to a small volume, causing sedimentation. The solid was collected to give N-(4-decyloxybenzyl)q 3 -benzo[d]oxazol-6-amine (16.5 g, 90%) as a colourless solid. , 48 millimolar) with a mixture of N-(4-decyloxyhanyl)_ι,3·benzo[expressin (1 3 g, 4.8 mmol) in a sealed tube at 14 (heated for 1 hour at rc. Allow the mixture to cool to Ambient temperature, during which time the precipitate is deposited. The solid is filtered 'washed with hexane and dried to give 6 (4 methoxybenzyl) _ 106H-[U] far spit and [5, 4 -eH嗓-7,8-dione (1.2 g, 76%), as an orange solid: NMR (300 MHz, DMSO-d6) 5 9.32 (s, 1H), 8.27 (d, J = 8.6 Hz, 1H), 7.37 (d, J = 8.6 Hz, 2H), 7.13 (d, J = 8.6 Hz, 1H), 6.86 (d, J = 8.6 Hz, 2H), 4.87 (s, 2H), 3.68 (s, 3H) 〇B. 8- via base-base group -2,3. dihydrogen from benzodioxantholine _6·yl)-like oxooxybenzyl)·6,8·dihydrotoxazol[ 5,4々]吲哚_7•辋 Synthesis According to the procedure as described in Preparation 2A, and irrelevant changes were made, using 2,3-di-ft-benzo-,4]dioxanthene Replace 3 desert 19 and use 6-(4-decyloxy T-based)_qing, 3M. Sit and [5,4 eH buds _7,8_dione replacement 143924-sp-20091127-2 -311 - 201020257 1-((5-(Tri-I-methyl)-fluorenyl-2-yl)methyl)dihydro-tooth-2,3_di-, to obtain 8-hydroxy-8-(7-hydroxy-2,3- Dihydro-l,4-benzodioxanthene-6(6)6(4methoxybenzyl)-6,8-dihydro-7H-[1,3Moxazolo[5,4 curry _7 ketone (39%), colorless Body: MS (ES +) m / z 477.1 (M + 1). c· 8_(7·transyl-2,3_dihydrogen from benzodioxol-6-yl) o-methoxybenzyl)-6,8·dihydro·7Η_[1,3&gt; Synthesis of oxazolo[5,4-e]indole-7-one According to the procedure as described in Preparation 4C, and irrelevant changes were made using 8-hydroxy-8-(7-hydroxy-2,3-di Hydrogen 4,4-benzodioxanthene,ylyl)_6_(4-methoxybenzyl)6,8-monohydro-7H-[1,3] oxazolo[5,4_e]sideside_7 _ketone replacement 4_gas ❹ --ι-(diphenylmethyl) each hydroxyl group (6-hydroxy 2,3 dihydrobenzophenanyl)_ U-dihydro-2H' p -2- Ketone 'obtained 8_(7_transyl 2,3_dihydro from benzodioxanthene-6-yl)-6-(4-methoxy-young 6,8-dihydro- qing, 3&gt ; 嗤 嗤 [5 4 e] 吲哚-7-one (89%), as a colorless solid: MS (ES+) m/z 46u (M + i). Preparation 100 3-[4-(Methoxy)- Synthesis of 2-phenylphenyl benzoyl) 4,3-dihydro-kappa-2嗣. 3_[4-(yloxy)-2.hydroxyphenyl]small(diphenylfluorenyl)·3 ·Hydroxyl. Synthesis of dihydrogen _2 吲 吲 朵 嗣 嗣 嗣 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 按照 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 合成 , , , , And using μ(diphenylfluorenyl)_吲哚吲哚-2,3-dione displaces 1-((5-(trifluoromethyl)pyran-2-yl)methyl)indoline_2 3_dione to give 3-[4- (benzyloxy)-2-hydroxyphenyl]small (diphenylmethyl)_3_hydroxy-u dihydro-2H-indol-2-one (75%) : MS (ES+) m/z 496.0 (M -17). Β·3·[4-(yloxy)-2-hydroxyphenylhydrazine (diphenylmethyl w,}dihydro·2H_吲哚_2·辋143924-sp-20091127-2 -312- 201020257 The synthesis is carried out as described in Preparation 4C, and irrelevant changes are applied, using [4-(loweroxy)_2_hydroxyphenyl η (diphenylhydrazinohydroxy- 13 dihydro-2h_aspartate) Displacement of 4-oxodiphenylhydrazinyl)3hydroxy-3-yl (6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)_1,3-dihydro-2H_indole-2-one, Obtained 3_[4&lt;benzyloxyhydroxyphenyl]-H-benzhydryl) 4,3-dihydro-2-indole, 哚_2-one (57%) as a colorless solid '111 surface 11 (300) (:13)5 9.01(8,111), 7.45-7.16(111,1511),7.13-7.01 (m, 2H), 6.96 (s, 1H), 6.85-6.76 (m, 1H), 6.71-6.65 ( m, 1H), 6.55-6.49 ® (m, 1H), 6.49-6·42 (m' !H), 5.10 (s, 1H), 4.99 (s, 2H). Preparation 101 3-[5-(section Synthesis of oxy)-2-hydroxyphenyl]-i-(diphenylfluorenyl) 4,3-di-argon-2]9;_吲哚_2-one A. 3-[5-(yloxy) Synthesis of _2_hydroxyphenyl]small (diphenylmethyl)·3_hydroxyw·dihydro-2h_p5丨哚-2-one according to the procedure as described in Preparation 2A, and irrelevant changes, ❷ use 4-(Oxygen Substituting 'replacement of 3-bromopan' and replacing 1-((5-(trifluoromethyl)pyran-2-) with 1-(diphenylindenyl)_ιη-Θ丨嗓-2,3-dione (indenyl) indoline-2,3-dione to give 3-[5-(ytoxy)-2-hydroxyphenylindole-(diphenylmethyl)-3-yl-1 3-Dihydro-2Η-indol-2-one (76%) : 4 NMR (300 MHz, CDC13) 5 8,63 (s,1Η), 7.46-7.40 (m, 1H), 7.38-7.21 (m , 15H), 7.13-7.06 (m, 2H), 6.97 (d, J = 8.8 Hz, 1H), 6.92 (s, 1H), 6.86 (dd, J = 8.8, 3.0 Hz, 1H), 6.52-6.45 ( m, 2H), 4.85 (s, 2H), 4.53 (s, 1H). Β·3·[5·(yloxy)·2-hydroxyphenyl]-1·(diphenylmethyl)-1, 3. Synthesis of dihydro-2H·啕哚_2·ketone 143924-sp.20091127-2 •313- 201020257 and irrelevant changes, benzyl)-3-hydroxy-1,3-dihydro-2H - using 3-[5-(non-oxy)-2-phenyl]-, (twenty-four-substituted 4-alkyl-η-di-methyl) groups according to the procedure described in Preparation 4C (4)-based 2,3-diazo-1-benzofuran-5-yl)-1,3-dihydro-2H-indole-2-one, obtaining 3_[5_(oxyl)2_benzene H-(diphenylhydrazinyl H,3_dihydro-2H to _2_ (67%), as a colorless solid: 1H dirty (300 hall, CDci3) ά 8 51 buckle s, m), 7 4i 7 i6 (m, qing, 7.10-7.03 (m, 2H), 7.02-6.97 (m, 1H), 6.96 (s, 1H) , 6.85-6.79 (m, 1H), 6.58-6.48 (m, 2H), 5.17 (s, 1H), 4.92 (s, 2H). Preparation 102 Synthesis of 1-(bromoindenyl)-2-(difluoroindenyl)benzene A. 1-(«-gasmethyl)-2·toluene Synthesis at ambient temperature in o-methylbenzene Add formaldehyde (diethylamino) sulfur trifluoride (6.70 g, 41.6 mmol) in anhydrous water in a solution of formaldehyde (500 g, 41.6 mmol) in anhydrous di-methane (50 mL) A solution of methane (3 mL). The mixture was stirred at ambient temperature for 16 h and a saturated aqueous The mixture was extracted with dioxane (2 χ 15 mL) and diethyl ether (100 mL). The combined organic phases were dried over sodium sulfate, filtered and dried in vacuo. The formed liquid was purified by column chromatography and eluted with dioxane to give 1-(difluoromethyl)-2-toluene (29 g, 49%) as a yellow liquid: 1H NMR (300) MHz, CDC13) 5 7.48 (d, J = 7.6 Hz, 1Η), 7.35 (dd, J = 7.0, 7.0 Hz, 2H), 7.24 (dd, J = 14.9, 7.6 Hz, 1H), 6.78-6.70 (m , 1H), 2.42 (s, 3H). Β· 1-(Xi-based fluorenyl)-2-(difluoromethyl)benzene synthesized in Ηdifluoromethyl)-2-indene benzene (2.90 g, 20.4 mmol) in four gasified carbon (50 N-bromosuccinimide (3 63 g, 20.4 mmol) and 2,2'-azobis (2-methylpropanenitrile) were added to the solution in 143924-sp-20091127-2 201020257 ml) ) (〇 167 grams, 1 〇 2 millimoles). The mixture was heated under reflux for 16 hours. An additional 2,2, azobis(2-methylpropanenitrile) (0.167 g, 1.02 mmol) was added and the mixture was heated at reflux for 4 h then cooled to ambient temperature with di-methane (175 Dilute with ML) and wash with water (2 X 175 mL) with saturated sodium sulphate (15 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The resulting residue was purified by column chromatography and eluted with ethyl acetate in dimethyl sulphate in dimethyl sulphuric acid to give 1-(bromomethyl)-2-(di) Fluoromethyl)benzene as a yellow solid: 1H NMR (300 MHz, CDC13) 5 7.58-7.56 (m, 1H), 7.43-7.37 (in, 3H), 6.95 (t, JH-F = 55.2 Hz, 1 Η) , 4.59 (s, 2H). Preparation 103 Synthesis of 3-(3-(difluoroindolyl)p-biti-2-yl]methylamide hydrochloride A. Synthesis of 3-(difluoromethyl)-2-methylpyridine in 2-methylpyridine -3-carboxyfurfural (3.8 g, 31.4 mmol) in dioxane (6 〇 10 mL), (diethylamino)sulfur trifluoride (4.14 mL, 31.4 mmol) . After 16 hours at ambient temperature, the reaction was quenched with EtOAc EtOAc (EtOAc) The organic phase was washed with brine (200 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with EtOAc EtOAc EtOAc (EtOAc) , as a yellow liquid: iHNMR (30 〇 MHz, CDC13) δ 8.58 (d, J = 4.8 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.21 (dd J = 7.8, 5.2 Hz, 1H) , 6.82-6.72 (m, 1H), 2.63 (s, 3H).

143924-sp-20091127-2 -315- 201020257 Synthesis of Β· 3-(difluoroindenyl)_2-mercaptopyridine small oxides at ambient temperature in 3-(difluoroindolyl) stilbene pyridine ( 2.56 g, 17.9 mmoles of 3-oxoperbenzoic acid (6.01 g, 26.8 mmol) in dioxane. After stirring for 2 hours, the mixture was diluted with a 1M aqueous sodium hydroxide solution (50 mL) and then evaporated. The organic phase was washed with brine (150 ml), dried over sodium sulfate sulfatesssssssssssssssssssssssssss 78%) : 1H NMR (300 MHz, CDC13) 5 8.36 (d, J = 6.5

Hz, 1H), 7.40 (d, J = 7.9 Hz, 1H), 7.23 (m, 1H), 6.80-6.70 (m, 1H), 2.57 (s, ® 3H). Synthesis of C·[3-(difluoromethyl)pyridine-2.yl]hydrazide hydrochloride 3-(difluoromethyl)-2-indenyl p to η-1-oxide 2.22 g, 14.0 mmol) with acetic anhydride (10 ml of '1 mM millimolar) at 8 (TC for 1 hour. Allow the reaction mixture to cool to ambient temperature, add diethyl ether (1 mL) and The mixture was washed with a 1M aqueous solution of sodium sulphate (1 mL), water (5 liters) and brine (5 liters). The organic layer was dried over sodium sulfate, filtered, and condensed in vacuo. Dissolved in decyl alcohol (70 ml), and added potassium carbonate (2 〇 2 gram, 14.6 mmol). The mixture was stirred at ambient temperature for 1 hour, concentrated in vacuo, and the residue was dissolved in water. And the extract is extracted with ethyl acetate (5 mL). The organic phase is washed with brine (1 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. By adding a 4m solution of hydrogenated hydrogen in 1,4-dioxanthine to make the product sink, [3-(difluoromethyl)P-pyridyl-2-yl]methylated hydrochloric acid Salt (〇.7〇〇克, 26%),

Is a colorless solid: 1H NMR (300 MHz, DMSO-d6) 5 9.89 (s, 2H), 8.81 (d, J 143924-sp-20091127-2 _316. (S) 201020257 =5.2 Hz, 1H), 8.44 (d , J = 7.6 Hz, 1H), 7.83 (m, 1H), 7.48-7.38 (m, 1H), 4.89 (s, 2H) 〇 Preparation 104 丄_(diphenylfluorenyl)-3-(5-hydroxy- 2,3-Dihydro-1,4-benzodioxanthene-based 嗓 嗓 调 调 调 Α 二 二 二 二 二 二 二 二 二 二 经 经 经 经 经 -3- -3- -3- -3- Synthesis of 3-dihydro-1,4-benzodioxol-6-yl)-1,3-dihydro-2-indole-2-one from 2,3-dihydro-1,4 - benzodioxanthene _5-alcohol (3.60 g, 23.7 mmol) © in hydrazine in anhydrous tetrahydrofuran (80 ml). Under the armpit, isopropyl magnesium chloride (11.8 ml, 2M solution in tetrahydrofuran, 23.7 mmol) was added. The mixture was stirred at TC for 45 min, concentrated in vacuo and EtOAc (EtOAc &lt;RTI ID=0.0&gt; a solution of 3-dione (4.94 g, 15.8 mmol) in 1 ,2-dichloroethane (7 mL). The reaction mixture was warmed to ambient temperature and stirred for 6 hrs and heated to 83 〇, and stirring for 3.5 hours. The reaction mixture was cooled to ambient temperature, concentrated in vacuo, and a saturated aqueous solution of ammonium chloride (25 mL) was added. The mixture was taken with ethyl acetate (250 ml, then 2 x 100 ml) The organic phase is washed with water (150 ml) and brine (150 ml), dried over sodium sulfate, and filtered, and the filtrate is concentrated in vacuo. The residue is dissolved in ethyl acetate. Hexane precipitates the solid to give μ(di-mercapto)-3-yl-3-(5-trans- 2,3-dihydro-1,4-benzodioxanthene-6- , 1,3-dihydroindol-2-indole-2-one (5.10 g, 69%) as colorless solid: iHNMR (300 MHz, CDC13) δ 9.14 (s, 1H), 7.43-7.30 (m , 9H), 7.22 (d, J = 8.7 Hz, 1H), 6.97-6.79 (m, 3H), 6.52 (s, 1H), 6.44 (d, J = 8.7 Hz, 1H) 6.26 (d, J = 7.8 143924-sp-20091127-2 - 317- 201020257

Hz, lH), 4.22 (s, 4H). B. 1-(Diphenylmethyl)-3-(5-hydroxy 4 q &amp;, 3·-hydro-1,4-benzodioxanthene. 6-yl) 1,3-dihydro- The synthesis of 2Η-〃5丨嗓-2-one is carried out according to the procedure described in Preparation 4C by ...&gt; | κ procedure' and the insignificant change is made using phthalic acid)-3-yl _3 Palladium-nitrogen-14-benzodiazepine dilute-6-yl)-1,3-dihydro-2Η-(tetra) phase replacement 4-gas-based (di-p-methyl) each vial-3-( 6-Carbyl-2,3-dihydro-1-benzopyran-5-yl-like diazo·2η__ _2嗣, obtains quinone I methyl)-3-(5-radio-2,3_2 Gas _14_benzodioxanthine sulphate, 3-dihydro-2 oxime, fluoren-2-one (82%), colorless solid: lH nmr (3〇〇MHz, DMSO-d6) (5 9.11 (s, 1H), 7.39-7.24 (m, 9H), 6.95-6.79 (m, 3H), 6.58 (d, J = 8.0 Hz, 1H), 6.35-6.30 (m, 2H), 4.21 (s, 4H) Preparation 105 1-(Diphenylmethyl)-3-(7-hydroxy-2,3-dihydro-!, winter benzodioxan-2-yl)_4,6-dimethoxy- Synthesis of 1,3-dihydro-2Η-β哚-2-one A. 1-(Diphenylmethyl)-4,6-dimethoxy_ιυ·ι»5卜多-2^3-二The synthesis of 嗣 is known, as described in the preparation of 26A, and the implementation does not matter The change, using 4,6-dimethoxy-1H-indole-2,3-dione to replace 2,3_dihydro-like]dioxanthene [2,3-fH丨哚- 7,8-dione, and the replacement of 2(bromomethyl)-5-(dimethylmethyl) with β-bromodiphenylmethane to obtain β-(diphenylmethyl)_4,6-dimethoxy Base-1Η-吲哚-2,3-dione (90%) : 1H NMR (300 MHz, DMSO-d6) 5 7.49-7.19 (m, 10H), 6.72 (s, 1H), 6.21 (d, J = 1.5 Hz, 1H), 5.87 (d, J = 1.5 Hz, 1H), 3.86 (s, 3H), 3.70 (s, 3H) B. 1-(Diphenylmethyl)-3-yl-3 -(7-radio-2,3-dihydro·1,4·benzodioxanthene-6-yl)-4,6-dimethoxy-1,3-dihydro-2Η-» »?卜朵-2·Web synthesis 143924-sp-20091127-2 -318- 201020257 According to the procedure as described in Preparation 2A, and the implementation of irrelevant changes, the use of 4- (toluene) replacement 3_ Bromophenol, and the use of μ(diphenylmethyl)_4,6-dimethoxy-1Η-啕哚-2,3-dione to replace iota((5-(trifluoromethyl)pyran-2-yl)methyl ) indoline-2,3-di-, obtained fluorene diphenylmethyl) each vial (7-trans-base 2,3_di-gas κ benzodioxanthene-6-yl)- 4,6-dimethoxy-1,3-dihydro-2Η-吲哚-2- Ketone (50%) ' is a colorless solid: iH NMR (3 〇〇 MHz, CDC13) 5 8.81 (s, 1 Η), 7.34-7.16 (m, 10H), 6.82 (s, 1H), 6.55 (s, 1H) , 6.31 (s, 1H), 6.14 (d, J = 1.8 Hz, 1H), 5.64 (d, J = 1.8 Hz, 1H), 4.22-4.10 (m, 4H), 3.92 (s 1H) 3 77 (s ❹ 3H), 3.49 (s, 3H). C· 1-(Diphenylmethyl)-3-(7•hydroxy.2,3_dihydro·1&gt;4 benzodioxanene·6_yl)·4,6·dimethoxy-1 ,3·Dihydro-2Η·&lt;indol-2-one synthesis According to the procedure as described in Preparation 4C, and irrelevant changes were made using 1-(diphenylfluorenyl)-3-carbyl-3 -(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene-6-yl)-4,6-dimethoxy-1,3-dihydro-2Η-choline 2-keto-substituted 4-yl-1-(diphenylfluorenyl)-3-yl-3-(6-hydroxy-2,3-dihydro-1-benzofuran-5-yl)-1 , 3-dihydro 10 -2Η-indol-2-one 'obtained bismuthylmethyl)-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene- 6-yl)-4,6-dimethoxy-1,3-dioxin-2-indole-2-one (92%) as colorless solid: 1H NMR (300 MHz, CDC13) δ 7.35-7.25 (m, 8Η), 7.21-7.14 (m, 2H), 6.87 (s, 1H), 6.61 (s, 1H), 6.27 (s, 1H), 6.17 (d, J = 1.8 Hz, 1H), 5.68 ( d, J = 1.8 Hz, 1H), 5.02 (s, 1H), 4.24-4.10 (m, 4H), 3.73 (s, 3H), 3.48 (s, 3H), 3.47 (s, 1H). Preparation of 106 H Diphenylhydrazinyl-3-(7-hydroxyindol-6-yl H,3-dihydro-2H-4indole-2-one Synthesis 143924-sp-20091127.2 -319- 201020257 Α· 1·(+Benzylmethyl)-3·经基·3·(7-经基峻喏-6-yl)·ΐ,3-diaza-2Η-Θ1 嗓-2·net synthesis at -40 °C to -30 ° C 'in porphyrin-6-alcohol (King et al; /. Ice plus C / xem. 1949: 3012.) (11.2 g '76.66 mmol) in tetrahydrofuran (80 〇 ml Add isopropylmagnesium hydride in a stirred solution (38.3 ml of 2.0 M THF solution, 76.60 mmoles p and stir the mixture at 0 °C for 2 hours, then add tetrahydrofuran (400 ml) 1_(diphenylfluorenyl)_1H_啕哚_2,3_dione (20.00 g '63.84 mmol). Mix the mixture at ambient temperature for 2 hrs and make the solution in saturated gasification The reaction was quenched and extracted with ethyl acetate (3×EtOAc). Purification by chromatography (dichloromethane / methanol, 100/1) to give 1-(diphenylmethyl)_3_hydroxy-3 -(7-hydroxyquinoxaline-6-yl)-1,3-dihydro-2H-indol-2-one (1 〇. gram, 34%) : 1H NMR (300 MHz, CDC13) 5 10.21 (s, 1H), 8.47 (s, 1H), 7.97-7.92 (m, 2H), 7.60-7.58 (m, 2H), 7.54-7.49 (m, 4H), 7.46-7.35 (m, 6H), 7 .U (s, 1H), 7.05-7.00 (m, 1H), 6.89-6.87 (m, 1H), 6.56-6.52 (m, 1H). Β·1·(diphenylmethyl)·3·(7 ·Hydroxyquinoxaline _6•yl) 4,3 dihydrogen 2H吲嗓^•Synthesis of steel at -10 ° C, in the second gasified sulfoxide (60 ml), add 1 (two stupid Methyl)-3-yl-3-(7-hydroxyquinoxalin-6-yl)-l,3-dihydro-2H-indole (3 g, 6.53 mmol). The reaction mixture was stirred at 0&lt;c&gt; and concentrated in vacuo. The residue was dissolved in ethyl acetate (15 mL) and then zinc powder (4.50 g, 68.81 mmol) was added. Mix for 40 minutes under ambient/JBL degree. Furnace, solid. Drain the liquid in vacuum 143924-sp-20091127-2 •320- 201020257 Dissolve the residue in ethyl acetate (200 ml) with water Wash with brine and dehydrated with anhydrous sodium sulfate 'And filtered. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography (di-methane / succinol 2 </RTI> / 1) to afford p(diphenylmethyl)-3-(7-hydroxyquinoxaline-6 -yl)-1,3-dihydro-2H-indol-2-one (2.40 g, 83%) ·* MS (ES+) m/z 444 (Μ + 1) ° Example 1 2-methylspiro Synthesis of bromo[2,3-f][l,3]benzo[s,3,3'-»»?丨嗓]-2'(1Ή)-one

In 1,3-bis(methyl)-3-(5-carbyl-2-methyl-1,3-indigo-indole)-1,3-dihydro-2Η-吲哚-2 - Ketone (1.70 g, 4.7 mmol) in a cooled (-78 ° C) solution in anhydrous tetrahydrofuran (30 mL), tris-n-butylphosphine (〇.8 mL, 5.7 mmol) The reaction mixture was then allowed to warm to ambient temperature &lt;RTI ID=0.0&gt;&gt;&gt; The reaction mixture was cooled to 〇 ° C ' and a 28% aqueous ammonia solution (1 mL) was added. The reaction mixture was stirred at 〇 ° C for 1 hour and acidified to pH 6 by dropwise addition of a 1% aqueous hydrochloric acid solution. The reaction mixture was extracted with EtOAc (EtOAc)EtOAc. The resulting solid was triturated with diethyl ether (5 mL). EtOAc EtOAc EtOAc EtOAc EtOAc -f][l,3]benzoxazole-7,3,-吲哚]-2'(1Ή)-one (1.03 g, 70%): melting point &gt;25 (TC (ethyl acetate); 4 NMR (300 MHz, DMSO-dg) 5 10.75 (br s, 1H), 7.89 (d, J = 8.6 Hz, 1H), 7.26- 143924-sp-20091127-2 -321- 201020257 7.19 (m, 1H), 7.10 (d, J = 8.6 Hz, 1H), 7.02-6.86 (m, 3H), 4.86-4.74 (m, 2H), 2.60 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.7 , 160.1, 148.9, 141.7, 138.5, 132.7, 128.6, 128.0, 123.4, 122.7, 122.1, 119.9, 109.7, 108.3, 80.9, 57.8, 20.0; MS (ES+) m/z 309,1 (M + 1). 1.1 14(6-Methylpyridin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8, Synthesis of 3'-吲哚]-2'(1Ή)-ketone

2,3-Dihydrospiro[吱,[2,3-§][1,4]benzodioxolene _8,3,_吲哚]_ 2(1 Η)-one (0.23克 '0.79 mmol, 6-mercapto-2-pyridol (0.13 g, 1.07 mmol) and triphenylphosphine (〇3 g, i 14 mmol) in benzene A solution of diethyl azodicarboxylate (〇22 g ' 1.27 mmol) in tetrahydrofuran) was slowly added to the mixture under nitrogen. The resulting mixture was stirred at ambient temperature for 16.5 hours. The solvent was removed under reduced pressure and the residue was evaporated mjjjjjjjjjjjjjj The combined organic solution was washed with brine (5 mL), dried over sodium sulfate. Purification by flash column chromatography using hexane/ethyl acetate (2:1) afforded Γ[[6-mercaptopyridine-2-yl) fluorenyl]-2,3-dihydrospiro[吱[2,3_g][14]benzodioxanthene·eucalyptus]2(1H)-one (0.13 g '41%) as a colorless solid: mp 183. 〇 (hex burned / B (4); 1H NMR (300 MHz, CDCl3) accounted for 7.56 (dd, j = 7 8, 7 5 Hz, out), 143924-sp-20091127-2 . -322 - (S) 201020257 7.23- 7.16 (m, 2H), 7.10-7.00 (m, 3H), 6.90 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.32 (s, 1H), 5.23 (d, J = 15.9 Hz , 1H), 4.958 (d, J = 9.0 Hz, 1H), 4.956 (d, J = 15.9 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.23-4.18 (m, 2H), 4.15 -4.11 (m, 2H), 2.59 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 177.8, 158.2, 155.4, 154.7, 144.8, 142.2, 138.4, 138.2, 132.3, 129.0, 124.0, 123.7, 122.9, 121.2, 118.8,

111.8.109.8, 99.6, 80.3, 64.7, 64.1, 58.3, 45.7, 24.1; MS (ES+) m/z 401.0 (M + 1). Example 1.2 ® 1'-(Pyridin-3-ylindenyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3M Synthesis of Budu]-2'(1Ή)-ketone

2,3-Dihydrospiro[furo[2,3-g][l,4]benzodioxene-8,3'-峋哚]-2'(1Ή)-steel (0.30 g , 1.00 mmol, 3-pyridyl alcohol (0.15 ml, 1.50 mM mil) and triphenylphosphine (0.36 g, 1.36 mmol) in a mixture of tetrahydrofuran (7 mL) under nitrogen A solution of diethyl azodiacetate (0.29 g ' 1.67 mmol) in tetrahydrofuran (3 mL) was slowly added. The resulting mixture was stirred at ambient temperature for 21 hours. The solvent was removed under reduced pressure and the residue was crystalljjjjjjjjjjjjj The combined organic solution was dried over sodium sulfate, dried and evaporated. The filtrate was purified by flash column chromatography using a methylene chloride/isopropanol (49:1, to 29:1) to obtain a mixture of the desired product and triphenylphosphine oxide. This material was acidified with 1 mL of EtOAc (30 mL) and EtOAc EtOAc EtOAc. The aqueous solution was made basic with 5M sodium hydroxide and extracted with dioxane (3 x 30 mL). Once dehydrated and dried over sodium sulfate, the organic solution was concentrated under reduced pressure to give bis-(acridin-3-ylmethyl)-2,3-dihydrospiro[furo[2,3-g][ 1,4]benzodioxanthene-8,3'-indole]-2'(1Ή)-one (0.22 g, 57%) as colorless solid: mp 142-143 ° C (ether / NMR (300 MHz, CDC13) δ 8.93-8.47 (m, 2H), 7.79 (d, J = 7.8 Hz, 1H), 7.45-7.36 (m, 1H), 7.23 (ddd, J = 7.8, 7.8, 0.9 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.19 (s, 1H), 5.09 (d, J = 15.8 Hz, 1H), 4.924 (d, J = 9.0 Hz, 1H), 4.919 (d, J = 15.8 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.22-4.17 (m, 2H), 4.14-4.09 (m, 2H); 13C NMR (75 MHz, CDC13) (5 177.8, 155.4, 148.0, 147.5, 144.9, 141.5, 138.5, 137.0, 132.2, 129.1, 124.3, 124.0, 120.8, 111.5, 109.0, 99.6, 80.2, 64.6, 64.0, 58.1, 41.7; MS (ES+) m/z 386.7 (M + 1). Example 1.3 1'-{[2 '5-Dimercapto-indole-(ι·decylethyl)_1H_p ratio _3_yl]methyl} snail [biting mers [2,3&lt;1[1'3] benzodioxanthene] Alkene_7,3,_ Indol] _21 (1 B) _ Synthesis of Gang

螺螺[吱,[2,3-f][l,3]benzodioxanthene _7,3,_吲哚] 2,(γη), (0.84 g, 3.0 mmol) and (1_isopropyl-2 5 dimethyl_ιηpyrrole) methanol (0.50 g '3.0 mmol) in anhydrous tetrazole (15 ml) in a solution of (iv), added tributyl Phosphine (〇9〇g, 丨5mmol). The solution was allowed to cool 143924-sp-20091127-2 -324- 201020257 but to 0C' and diethyl azodicarboxylate (0.78 g, 4.5 mmol) was added. The solution was stirred at ambient temperature for 16 h then quenched with saturated EtOAc (EtOAc) The aqueous solution was extracted with ethyl acetate (2 mL), dried over Celite &lt; The residue was purified by flash chromatography using ethyl acetate (15% to 50% gradient) hexanes to give 1, _{[2,5-didecyl fluorenylethyl)-1H _pyrroleyl]methyl}spiro[吱,[2,3-f][l,3]benzodioxolene-7,3,-accelene]-2'(1Ή)-one ( 0.32 g '24%) ' is a colorless solid: melting point 169_m〇c; iHNMR (3〇〇MHz, © CDC13) δ Ί.2Ί-Ί.20 (m, 1Η), 7.11 (d, J = 7.5 Hz, 1H ), 7.02-6.95 (m, 2H), 6.49 (s, 1H), 6.09 (s, 1H), 5.85-5.82 (m, 2H), 5.77 (br s, 1H), 4.77 (ABq, 2H), 4 , 69 (ABq, 2H), 4.37 (seven peaks, J = 7.0 Hz, 1H), 2.33 (s, 3H), 2.22 (s, 3H), I. 43 (d, J = 7.0 Hz, 6H); 13C NMR (75 MHz, CDC13) δ 194.7, 177.2, 155.9, 148.7, 142.9, 142.2, 132.5, 128.7, 127.0, 125.5, 123.6, 122.9, 119.9, 113.0, 109.6, 107.6, 103.2, 101.4, 93.5, 80.5, 58.2, 47.3, 37.0, 22.2, 14.1, II. 5 ; MS (ES+) m/z 431.20 (M + 1).

Example 1.4 5-(decyloxy)-l'-[(5-carbyl-2-thienyl)methyl]spiro[1-benzofuran_3,3,_w 哚]-2\ΓΗ)-one Synthesis

3-[5-(indolyl)-2-phenyl]-1-[(5-chloro-2-t»septyl)indenyl]-indolyl-1,3-dihydro -2H-indol-2-one (2.71 g, 5.52 mmol) in a stirred solution of anhydrous tetrahydrofuran (60 mL), tributylphosphine (139 g, 143924-SP-20091127-2) • 325- 201020257 6.90 millimoles). The solution was cooled to οχ: and di-tert-butyl azodicarboxylate (1.59 g, 6.90 mmol) was added. The solution was stirred at 〇〇c for 2 min, then quenched with 10% aqueous HCI (50 mL). The aqueous solution was extracted with ethyl acetate (3.times.100 mL), brine (3.times.50 ml), dried over anhydrous sodium sulfate, filtered, and concentrated to dryness in vacuo. The residue was purified by flash column chromatography using ethyl acetate (2%) in hexanes to give 5-(+oxy)-indole-[(5-carbyl-2-p. )methyl] snail [ι_benzopyrene _3,3,·ρ5丨哚]-2'(1Ή)-嗣(2.36 g, 90%) ' is a colorless solid: melting point ^2-1351; 1H NMR (300 MHz, DMSO-d6) 5 7.33-7.21 (m, 7 Η), 7.16-7.12 (m, 2 Η), 7.02 β (ddd, J = 7.4, 7.4, 1.0 Hz, 1H), 6.97 (d, J = 3.8 Hz, 1H), 6.90-6.32 (m, 2H), 6.21 (d, J = 2.3 Hz, 1H), 5.05 (ABq, 2H), 4.82 (s, 2H), 4.72 (ABq, 2H) ; 13 c NMR (75 MHz, DMSO-dg) 5 176.6, 155.0, 153.6, 141.9, 138.6, 137.4, 132.0 130.3, 129.4, 128.8, 128.2, 128.1, 127.9, 127.1, 124.3, 123.8, 116.6, 110.8, 110.0, 109.9, 79.4, 70.4, 58.1, 38.9; MS (ES+) m/z 476.3 (M + 1), 474.3 (M + 1). Example 1.5 Synthesis of -bromospiro[吱,[2,3-f][l,3]benzodioxanthene-7,3,-吲哚]-2,(1Ή)·anthracene

At 0 C, '7-glycine-3-(6-carbyl-1,3-n-dioxy-oxo_5_yl)_3_(hydroxymethyl)-1,3-dihydro-2Η -Chroin-2-one (4.70 g, 12.4 mmol) in suspension in anhydrous tetrahydrofuran (120 mL), added tributylphosphine (3 8 -326- 143924-sp-20091127-2 (S ) 201020257

ML, 15.5 mmol, followed by the addition of di-tertiary-butyl azodicarboxylate (3.58 g, 15.5 mmol) in anhydrous tetrahydropyran (25 mL). The reaction mixture was stirred at 0 °C for 1 hour and at ambient temperature for 16 hours. The reaction was quenched by EtOAc (EtOAc) (EtOAc) The combined organics were washed with brine (1 mL) dried over anhydrous sodium sulfate. The residue was purified by column chromatography using ethyl acetate (10% to 30% gradient) to afford 7'-bromo snail [2,3-f][l,3 Benzodioxanthene β-ene-7,3·-啕哚]-2'(1Ή)-one (2.4 g, 53%) as colorless solid: melting point 240 ° C (decomposition); 1H NMR (300 MHz, DMSO-d6) 5 10.88 (s, 1H), 7.34 (dd, J = 8.1, 1.0 Hz, 1H), 7.10 (d, J = 7.2 Hz, 1H), 6.93 (dd, J = 8.1, 7.5 Hz , 1H), 6.68 (s, 1H), 6.36 (s, 1H), 5.93 (dd, J = 2.9, 0.8 Hz, 2H), 4.77 (d, J = 9.4 Hz, 1H), 4.65 (d, J = 9.4 Hz, 1H) ; 13 C NMR (75 MHz, DMSO-d6) δ 178.1, 155.3, 148.2, ❹ 141.6, 141.1, 134.2, 131.4, 123.8, 122.8, 119.4, 103.1, 102.0, 101.3, 93.1, 79.9, 58.8 MS (ES+) m/z 360.2 (M + 1), 362.2 (M + 1); MS (ES-) m/z 358.2 (M-1), 360.2 (M -1). Example 1.6 Γ-[(3-Isoisoxazol-5-yl)indolyl] snail [bito-and-[2,3-f][l,3]benzodioxanthene-7,3 ·-嗍哚]-2'(1Ή)-ketone synthesis

〇&gt; 〇h3c to (3-isopropylisoxazol-5-yl)methanol (0.338 g, 2.4 mmol) at N,N- 143924-sp-20091127-2 -327- 201020257 dimethyl In an ice-cold stirred suspension of decylamine (20 ml), add gasified N-(carbymethylidene)_N_mercaptoamine salt (〇36 g, 2 8 mmol) in N,N_ A solution of decylamine (10 ml). The mixture was spoiled at ambient temperature for 30 minutes' and then transferred to snail [吱 并 3 ] benzodioxos-7-3'- 吲哚]-2'(1 Ή)-one (0.56 g, 2.0 Milliol), carbonated planer (1.95 g, 6.0 mmol) in suspension of hydrazine, hydrazine-dimethylformamide (4 mL). The reaction mixture was stirred at ambient temperature for 16 h and filtered. The solid was washed with acetone (100 mL). The filtrate was concentrated in vacuo. Purification of the residue by column chromatography 'ethyl acetate (1% to 3% by weight gradient) to obtain 1·-[(3-isopropylisoxazole-5-yl) Scorpion] snail [吱,[2,3-f][l,3] benzodioxolan-7,3·-啕哚]-2'(1Ή)-one (0.50 g, 60%) , as a colorless solid: m.p. 132-136 ° C (diethyl ether / hexanes); 1H NMR (300 MHz, DMSO-d6) δ 7.34 (ddd, J = 7.7, 7.7, 1.2 Hz, 1H), 7.21 (d, J = 7.5 Hz, 1H), 7.14 (d, J = 7.7 Hz, 1H), 7.08 (ddd, J = 7.5, 7.5, 0.8 Hz, 1H), 6.71 (s, 1H), 6.49 (s, 1H), 6.21 (s, 1H), 5.93 (d, J = 1.0 Hz, 2H), 5.08 (s, 2H), 4.82 (d, J = 9.4 Hz, 1H), 4.72 (d, J = 9.4 Hz, 1H), 3.03 (m, 1H), 1.19 (d, J = 6.9 Hz, 6H); 13 C NMR (75 MHz, DMSOO (5 176.4, 168.9, 166.3, 155.2, 148.3, 141.6, 141.5, Cao 131.4, 128.8, 123.6, 123.2, 119.5, 109.1, 102.8, 101.3, 101.1, 93.2, 79.5, 57.2, 35.6, 25.8, 21.2; MS (ES+) m/z 405.3 (M + 1). Example 1.7 Γ-[(4-bromo-2 - 喽 基 曱 ] ] ] 吃 [[,,,,,,,,,,,,,,,,,,,, Synthesis -328- 143924-sp- 20091127-2 (8) 201020257

Following the procedure as described in Example 1.6, and performing an insignificant change's replacement of (3-isopropylisoxazol-5-yl) decyl alcohol with (4-bromo-pyrimidin-2-yl) decyl alcohol, Obtained 14(4-bromo-2-pyrimenyl)methyl]spiro[misano[2,3-f][l,3]benzodioxene-7,3·-吲哚] -2·(1Ή)-one (47%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) (5 7.59 (d, J = 1.5 Hz, 1H), 7.35-7.18 (m, 4H), 7.06 (ddd, J = 7.4, 7.4, 0.7 Hz, 1H), 6.71 (s, 1H), 6.12 (s, 1H), 5.93 (d, J = 2.2 Hz, 2H), 5.11 (d, J = 6.9 Hz , 2H), 4.81 (d, J = 9.4 Hz, 1H), 4.70 (d, J = 9.4 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) δ 176.5, 155.4, 148.4, 141.7, 141.4, 140.9 , 131.6, 129.2, 128.9, 123.8, 123.7, 123.3, 119.6, 109.4, 108.0, 102.7, 101.5, 93.4, 79.7, 57.4, 38.1 ; MS (ES+) m/z 478.1 (M + 23), 480.1 (M + 23 Example 1.8 Γ-(1-benzofuran-2-ylindenyl) snail [&gt; Furano[2,3-f][l,3]benzodioxanthene φ _7,3· -吲哚]·2'(1Ή)-ketone synthesis

The hydrazine-(1-benzene) was obtained by substituting benzofuran-2-ylmethanol (3-isopropylisoxazole-5-yl)methanol according to the procedure described in Example 1.6 and performing an insignificant change. And furan-2-ylmethyl) snail [ρ 喃 并 笨 笨 二 二 二 二 -7 -7,3'-θ 丨 noise]-2' (1Ή)-net (44%), is a colorless solid: melting point 167_16yc (B 143924-SD-20091127-2 201020257 ether); 1H NMR (300 MHz, DMSO-d6) (5 7.60 (dd, J = 7.0, 1.5 Hz, 1H), 7.50 (d, J = 8.2 Hz, 1H ), 7.33-7.19 (m, 5H), 7.05 (ddd, J = 7.4, 7.4, 0.9 Hz, 1H), 6.98 (s, 1H), 6.72 (s, 1H), 6.22 (s, 1H), 5.94 ( d, J = 4.3 Hz, 2H), 5.15 (d, J = 6.0 Hz, 2H), 4.84 (d, J = 9.4 Hz, 1H), 4.73 (d, J = 9.4 Hz, 1H); 13 C NMR ( 75 MHz, DMSO-d6) δ 176.5, 155.3, 154.3, 152.2, 148.4, 141.8, 141.7, 131.6, 128.8, 127.8, 124.4, 123.6, 123.2, 123.0, 121.1, 119.7, 110.9, 109.5, 105.2, 102.9, 101.5, 93.3, 79.7, 57.5, 37.2; MS (ES+) m/z 412.3 (M + 1). Example 1.9 Γ-{[2-mercapto-5-(trifluoromethyl)·ι, 3_α azole _4_螺 } } } 螺 2 2 2 [2,3-f][l,3] benzodioxene _7,3' _峋哚]-2'(1Ή)-ketone synthesis

Under 〇 °C, snail [M-benzo benzodioxene '3,-吲哚]-2 (1Ή)- Stirring 1 (〇, 281 g, 1. 〇 millimol) and (2 _Methyl_5 (trifluoromethylidene-4-oxazol-4-yl)nonanol (0.18 g, L0 mmol) in a mixture of anhydrous tetrahydrofuran (8 mL),

Ethyl acetate (1% by weight 143924-sp-20091127-2) in hexane was used, followed by the addition of a rebel amine (0.26 g, 1.5 mmol). It will be returned to the hour and stirred at ambient temperature for 16 hours. 50 ml) The reaction mixture was quenched with vinegar. The combined organic solution was dried with brine (3 hr dry, and concentrated in vacuo to dry-330·201020257 to 30% gradient) to give Γ-{[2-methyl-5-(trifluoromethyl) )-1,3-oxazol-4-yl] fluorenyl} snail [吱,[2,3-f][l,3]benzodioxol-7,3'-啕哚]- 2·(1Ή)-copper (0.30 g, 68%), as a colorless solid, melting point 136-137 ° C (diethyl ether/hexane); NMR (300 MHz, DMSO-d6) δ 7.32 (ddd, J = 7.7 , 1.2, 1.2 Hz, 1H), 7.19 (dd, J = 7.6, 1.0 Hz, 1H), 7.07-7.03 (m, 2H), 6.70 (s, 1H), 6.29 (s, 1H), 5.93 (dd, J = 5.0, 0.7 Hz, 2H), 4.98 (q, J = 16.4 Hz, 2H), 4.75 (dd, J = 20.8, 9.4 Hz, 2H), 2.46 (s, 3H) ; 13CNMR (75MHz, DMSO-d6 5 176.5, 163.6, 155.1, 148.2, 141.9, 141.5, 137.6 (d, 3JCF = 2.1 Hz), 133.5 (q, 2JCF = 42.7 Hz), 131.6, ❹ 128.7, 123.5, 123.0, 119.8, 119.2 (q, 266.9 Hz), 109.0, 103.0, 101.3, 93·1, 79.3, 57·2, 34.9, 13.4; MS (ES+) m/z 445.3 (M+l). Example 1.10 (3R)-5,6-Dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3,-indole]-2,(1Ή)-one and Synthesis of (3S)-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3·-啕哚]-2,(1Ή)-one

(foot) (s) 5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]difuran-3,3,-θ丨哚]-2,(1Ή)- The ketone (0.04 g) was dissolved 'and heated, and sonicated in diterpenoid (03 ml). Acetonitrile (0.3 ml) and decyl-tert-butyl ether (2.0 ml) were added, and the mixture was subjected to a submicron transition. The mixture was injected into a Waters LC/MS automated purification system (Waters) containing CHIRALPAK-IA (West Chester, PA) HPLC column (21 mm id X 25 〇 mm length, 20 μm particle size). Company, Milford, MA) was dissolved in methyl tri-butyl ether/acetonitrile (9/1) at a flow rate of 15 ml / 143924-sp-20091127-2 -331 - 201020257 min, using 254 Uv detection at nanometers, after 2 minutes of operation time. 35 repeated injections were carried out under these conditions, which corresponded to a total of 1.40 g of the racemate. After the resolution, the appropriate fractions were concentrated in vacuo to dryness &lt;&quot;&quot;&quot;&quot; The first dissolving parasol is (3S)-5,6-dihydrospiro[benzo[^7:5.4-b]difuran-3,3'-啕哚]-2'(1Ή) a ketone which is obtained as a colorless solid with a 67% recovery (0.472 g): mp 255-256 Χ: (methanol); 1H NMR (300 MHz, DMSO-d6) δ 10.56 (br s,1 Η), 7.26 -7.18 (m,1Η), 7.09 (d,J = 6.9 Ηζ, ❹ 1H), 6.98-6.89 (m, 2H), 6.49 (s, 1H), 6.38 (s, 1H), 4.77 (d, J = 9.2 Hz, 1H), 4.65 (d, J = 9.2 Hz, 1H), 4.52-4.43 (m, 2H), 2.99-2.91 (m, 2H) ; 13C NMR (75 MHz, DMSO-de) δ 178.7, 131.0 , 160.6, 141.8, 133.0, 128.6, 123.8, 122.3.120.8.119.7.119.0. 109.7, 92.4, 79.9, 72.1, 57.3, 28.4; MS (ES+) m/z 278.0 (M + 1). The second dissolving parasol is (3R)-5,6-dihydrospiro[{,2-b: 5.4-b']difuran-3,3'-吲哚]-2 '(1Ή)-ketone, which is obtained as a colorless solid with ❹ with 60% recovery (0.423 g): mp 256-257 ° C (yield); 1 H NMR (300 MHz, DMSO-d6) δ 10.56 (br s, 1H), 7.26-7.18 (m, 1H), 7.09 (d, J = 6.9 Hz, 1H), 6.98-6.89 (m, 2H), 6.49 (s, 1H), 6.38 (s, 1H ), 4.77 (d, J = 9.2 Hz, 1H),

4.65 (d, J = 9.2 Hz, 1H), 4.52-4.43 (m, 2H), 2.99-2.91 (m, 2H); 1 3C NMR (75 MHz, DMSO-d6) &lt;5 178.7, 131.0, 160.6, 141.8, 133.0, 128.6, 123.8, 122.3.120.8.119.7.119.0. 109.7, 92.4, 79.9, 72.1, 57.3, 28.4; MS (ES+) m/z 278.0 (M + 1). Example 1.11 143924-sp-20091127-2 •332· (S) 201020257 (R)-3,7-monohydro-2H-spiro[benzofuro[5,6 b][1,4]dioxane Alkene-8,3,dihydrogen

Dioxetene

Dissolve 2,3-dihydrospiro[c, s[2,3_g][l,4]benzodioxolene _8 3, _啕φ哚]_2'(1Ή)-_ (0.14 g) In hot dimethyl hydrazine (〇. 4 ml). Acetonitrile (0.4 ml) and decyl-tert-butyl ether (22 ml) were added, and the mixture was filtered through sub-micron. The mixture was injected into a Waters LC/MS automated purification system (Waters, Inc., equipped with cmRALpAK_IA (West Chester, PA) HPLC column (30 mm id X 250 mm length, 2 〇 micron particle size). Milford, ΜΑ), and eluted with methyl third-butyl ether/acetonitrile (98/2) at a flow rate of 3 〇 ml/min 'detected using 254 254 at 254 nm for 6 〇 minutes Operating time. After the resolution, the appropriate fractions were concentrated in vacuo to φ dryness, and the solid formed was triturated with water (30 ml), collected by vacuum filtration, and dried under high vacuum. The first dissolving parasol is (R) 2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxene _8,3W丨哚] _2·(1Ή)-ketone, which is obtained as a colorless solid; 1 H NMR (300 MHz, DMSO-d6) 5 10.57 (s, 1 Η), 7.24 (ddd, J = 7.7, 7.7, 1.0 Hz, 1H), 7.09 (d, J = 6.9 Hz, 1H), 6.96 (dd, J = 7.5, 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.16 (s, 1H) ), 4.73 (d, J = 9.0 Hz, 1H), 4.60 (d, J = 9.0 Hz, 1H), 4.20-4.15 (m, 2H), 4.12-4.07 (m, 2H) ; MS (ES+) 143924- Sp-20091127-2 -333 - 201020257 m/z 296.0 (Μ + 1) ; [ cc] D-36.61 (c 1.0, DMSO). The second dissolving parasol is (S)-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxene-8,3'-吲哚]-2'(1Ή)-one, which was obtained as a colorless solid; 1H NMR (300 MHz, DMSO-d6) &lt;5 10.57 (s, 1 Η), 7.24 (ddd, J = 7.7, 7.7.1.0 Hz, 1H), 7.09 (d, J = 6.9 Hz, 1H), 6.96 (dd, J = 7.5, 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.16 (s, 1H), 4.73 (d, J = 9.0 Hz, 1H), 4.60 (d, J = 9.0 Hz, 1H), 4.20-4.15 (m, 2H), 4.12-4.07 (m, 2H) ; MS (ES+) m/z 296.0 (M + 1); [a]D+ 36.65 (c 1.0, DMSO). Example 1.12 φ (83)-1'-{[3-(Trifluoromethyl)&gt;biti-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g] Synthesis of [l,4]benzodioxanthene-8,3'-θ丨嗓]-2'(1Ή)-_

(3-(Di-Imethyl) ρ-But-2-yl)methanol hydrochloride (5.0 g, 23.14 mmol) and di-vaporized sulfite (5.0 g, 42.0 mmol) in two gas In a mixture of decane (5 liters of liters), add two drops of hydrazine, Ν: methylmethalamine at (TC). Allow the reaction mixture to warm to ambient temperature and stir for 16 hours under reduced pressure. The solvent was removed and the residue was dissolved in hydrazine, hydrazine-dimethylamine (5 mL). To the above solution, (8S)_2,3_dihydrospiro[[, 3 g][i 4]benzodioxanthene-8,3,-呻哚]-2|(1Ή)·one (4·72 g, 15 98 mmol), cesium carbonate (16.3 g' 5_mole) and 峨化峰〇克, 6〇mole). The reaction mixture was allowed to warm to a surface and stirred under nitrogen for 2.5 hours. The reaction was allowed to mix 143924-sp-20091127-2 334 (S) 201020257. The material was cooled to ambient temperature, concentrated to dryness under reduced pressure, and the residue was treated with water (50 ml) and sonicated for 0.5 hour. The suspension was filtered, washed with water (50 ml) and dried The solid crude product was subjected to column chromatography using dichloromethane/ethyl acetate (1:100-1:4) to give (8S)_r_{[3_(trifluoromethylindole-2-yl)methyl} -2,3-二氲螺[吱,[2,3-g][l,4]benzodioxanthene, -8,3'-吲]-2'(1Ή)-ketone (5.45克, 75%), as a colorless solid: mp 164-165 ° C (yield); 1H NMR (300 MHz, DMSO-d6) 5 8.62 (d, J = 4.4

Hz, 1H), 8.20 (d, J = 7.7 Hz, 1H), 7.51 (dd, J = 7.7, 5.0 Hz, 1H), 7.23-6.82 β (m, 4H), 6.47 (S, lH), 6.43 ( s, lH), 5.21 (ABq, 2H), 4.73 (ABq, 2H), 4.18-4.04 (m, NMR (75 MHz, DMSO-d6) 5 177.5, 155.0, 152.9, 152.8, 144.5, 143.3, 138.2, 135.5 , 135.4, 132.4, 129.1, 126.1, 124.1, 123.9, 123.7, 123.4, 123.3, 122.8, 122.5, 122.0, 112.2, 109.4, 99.0, 79.6, 64.6, 64.0, 57.7, 42.4, 42.3 ; MS (ES+) m/z 454.9. Example 1.13 (8S)-l'-[(5-Pyridyl-p-But-2-yl)methyl]-2,3-dihydrospiro[吱n南和[2,3_g][i,4 Synthesis of benzodioxanthene-8,3^吲哚]-2'(1'11)-one

(8S)-2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3W丨哚]-2'(1Ή)-one (1.3 g '4.4 mmol), (5-(yloxy) acridine-2-yl)methanol (1.23 g, 5.72 mmol) and tributylphosphine (1.26 g, 6.23 mmol) A mixture of tetrahydrol-pyran (150 ml) was added with azobis-acidic acid-acetic acid (U5 g ' 6.62 mmol) at 0 °C. The reaction mixture was allowed to warm to ambient temperature 143924-sp-2009 1127-2 -335 - 201020257 and stirred for 48 hours. The reaction mixture was diluted with ethyl acetate (1 mL) and filtered and evaporated. The residue was dissolved in di-methane (150 ml), washed with 1M hydrochloric acid (3········· Concentrate to dryness. The residue was sonicated with methanol (3 mL), and the solid product was filtered to give (8S)-l,-{[5-(;oxycycloazin-2-yl)indolyl 2,3_ Dihydrospiro[,,,,,,,,,,,,,,, ((8S)-l,-{[5-(- yloxy aridin-2-yl)methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4 Benzodioxanthene _8,3'-啕嗓]-2,(1Ή)-one (1.54 © g' 3.12 mmol) with ammonium formate (1. gram, 15.86 mmol) Add 10% palladium on carbon (0.5 g) in a mixture of decyl alcohol (5 mL). The reaction mixture was heated under reflux with nitrogen for 1 hour. The reaction mixture was cooled to ambient temperature, filtered and filtered. Concentration under pressure. The residue was subjected to column chromatography using dichloromethane-methanol (20:1 to 10:1) to give (8S)-r-[(5-hydroxypyridin-2-yl)methyl ]-2,3-di-argon snail [bito-and-[2,3-g][l,4]benzodioxolene-8,3·-吲哚]-2·(1Ή)-one ( 0.93 g, 50%), as colorless solid: m.p. 256-258 Χ: (m.p.-hexane); iHNMROOO MHz. DMSO-A) 8.51 (s, lH), 7.96 (d) , J = 2.7 ®

Hz, 1H), 7.23-6.85 (m, 6H), 6.45 (s, 1H), 6.34 (s, 1H), 4.97 (ABq, 2H), 4.79 (ABq, 2H), 4.08-3.91 (m, 2H) , 3.78-3.56 (m, 2H) ; 13C NMR (75 MHz, DMSO-d6) δ 178.4, 155.3, 152.9, 145.7, 144.6, 142.2, 138.3, 137.3, 132.1, 128.8, 124.3, 124.0, 123.7, 122.5, 120.5 , 111.7, 109.5, 99.4, 79.7, 64.4, 63.4, 58.2, 44.9; MS (ES+) m/z 402.8 (M + 1). Example 1.14 14(5-indolylpyridin-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodiazepine 143924-sp-20091127- 2 - 336- (S) 201020257 Oxygen decene _8,3'-W哚]-2, (m)-ketone: synthesis

The (10)-bromopyridin-2-yl)methyl group was obtained by substituting (5-bromopyridin-2-yl)methanol for 3-pyridine methanol according to the procedure as described in Example 1.2 and carrying out an insignificant change. ]-2,3-dihydrospiro[[,,,,,,,,,,,,, ), as a colorless solid: melting point 2〇1_2〇rc; 1hnmr β (300 MHz, CDC13) δ 8.63 (d, J =: 2.4 Hz, 1H), 7.79 (dd, J = 8.4, 2.1 Hz, 1H), 7.24 -7.16 (m, 3H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.28 (s, 1H), 5.15 ( d, J = 15.9 Hz, 1H), 4.94 (d, J = 9.0 Hz, 1H), 4.91 (d, J = 15.9 Hz, 1H), 4.67 (d, J = 9.0 Hz, 1H), 4.22-4.11 ( m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 177.5, 155.3, 154.1, 150.6, 144.7, 141.9, 139.7, 138.3, 132.2, 128.9, 123.9, 123.6, 123.1, 121.0, 119.9, 111.6, 109.4, 99.4 , 80.1, 64.5, 63.9, 58.1, 45.5; MS (ES+) m/z 465.1 (M + 1), 467.1 (M + 1). φ Example 1.15 Γ-{[5-(4-Phenylphenyl)-2-(trifluoromethyl)furan-3-yl]methyl} snail [bite-and-[2,3-f][l,3 Synthesis of benzodioxanthene _7,3^?丨哚]-2\1Ή)-ketone

Following the procedure as described in Example 1.6, and carrying out an insignificant change, using (5-(4-oxaphenyl)_2-(trifluoromethyl)furan-3-yl)methanol (3-isopropyl 143924-sp-20091127-2 • 337 - 201020257 Isoxazol-5-yl) decyl alcohol, which gives 1·-{ [5-(4-phenylphenyl)-2-(trifluoromethyl)furan-3- Sulphur [furan[2,3-f][l,3]benzodioxol-7, 吲崃]-2'(1Ή)-嗣, (35%), colorless Solid: melting point 114-116°C; iHNMRQOOMHz, CDC13) δ 7.55 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.7 Hz, 2H), 7.28 (dd, J = 7.8, 7.8 Hz, 1H ), 7.18 (d, J = 7.5 Hz, 1H), 7.06 (dd, J = 7.5, 7.5 Hz, 1H), 6.87 (d, J = 7.8 Hz, 1H), 6.57 (s, 1H), 6.53 (s , 1H), 6.09 (s, 1H), 5.87 (s, 2H), 4.96 (ABq, 2H), 4.82, (ABq, 2H) ; 13 C NMR (75 MHz, CDC13) δ 177.8, 156.0, 155.2, 149.1 , 142.4, 141.4, 137.7, 135.1, 131.9, 129.2, 129.1, 127.8, 127.1, 125.9, 124.7, 124.2, 123.9, 121.6, 119.2, 113.9, 108.6, 106.6, 102.8, 101.6, ® 93.8, 80.3, 58.2, 34.4; MS (ES+) m/z 540.3 (M + 1), 542.3 (M + 1). Example 1.16 Γ-{[5-Alkyl-1-methyl-3-(trifluoromethyl)-1Η-pyrazol-4-yl]indenyl} snail [taste and [2,3-f][ Synthesis of l,3]benzodioxanthene-7,3'·蚓哚]-2'(1Ή)-_

(5-Alkyl-1-methyl-3-(trifluoromethylindole-pyrazol-4-yl)methanol (Nakatani et al.) was used according to the procedure described in Example 1.6 and insignificantly changed. , EP 2002/743670) Displacement of (3-isopropylisoxazol-5-yl)methanol to give Γ-{[5-yl-1-methyl-3-(trifluoromethyl)-1H-pyridyl Oxazol-4-yl]methyl} snail [c-butyl[2,3-f][l,3]benzodioxol-7,3'-(5)哚]々'(ΓΗ)-one ( 70%), as a colorless solid: m.p. 180-182 ° C; WNMR (300 MHz, CDC13) δ 7.26-7.12 (m 2 Η) 7.03 (dd, J = 7.5, 7.5 Hz, 1H), 6.75 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.14 (s, 143924-sp-20091127-2 . 338 . (S) 201020257 1H), 5.84 (d, J = 5.3 Hz, 2H), 4.92 (s, 2H), 4.75 (ABq, 2H), 3.86 (s, 3H); 1 3 C NMR (75 MHz, CDC13) &lt;5 177.3, 156.2, 148.9, 142.4, 141.6, 139.6 (q, J = 37.9 Hz), 132.0, 128.9, 128.7, 124.1, 123.6, 122.7, 119.0, 110.6, 108.9, 103.4, 101.5, 93.6, 80.9, 58.2, 37.2, 33.5 ; MS (ES+) m/z 478.3 (M + 1), 480.3 (M + 1). Example 1.17 曱oxypyridin-3-yl) snail [吱,[2,3-f][l,3]benzodioxolene Synthesis of -7,3'-啕哚]-2·(1Ή)-ketone

In a 10 ml pressure-resistant tube, the snail [吱,[2,3-f][l,3]benzodioxanthene-7,3W丨哚]-2,(1Ή)-_ (0.28) Gram, 1.0 mmol, 3-bromo-5-methoxypyridine (0.26 g, 1.4 mmol), palladium acetate (II) (0.038 g, 0.2 mmol), 9,9-dioxin 4-,5-bis(diphenylphosphino)dibenzopyran (0.14 g, 0.24 毫 millimolar), carbonic acid planer (0.46 g, 1.4 mmol) and 1,4-dioxane (1.2 ml). The reaction mixture was heated under microwave irradiation for 15 minutes at TC and allowed to cool to ambient temperature. The mixture was diluted with dichloromethane (2 mL) and filtered through a pad of Celite. Concentration in the residue and purification of the residue by column chromatography, eluting with ethyl acetate in hexane to 5% to 15% gradient to give 1,-(5-methoxypyridin-3-yl) snail [吱吱[2,3-f][l,3]benzodioxol-7,3'-吲哚]-2'(1Ή)-_ (0.097 g, 25%), brown Solid: 4 NMR (300 MHz, CDC13) 5 8.37 (d, J = 6.2 Hz, 2H), 7.39-7.34 (m, 1H)' 7.32-7.24 (m, 2H), 7.18-7.09 (m, 1H), 6.95 (d, J = 7.9 Hz, 1H), 6.53 (s, 143924-sp-20091127-2 -339 - 201020257

1H), 6.25 (s, 1H), 5.88 (d, J = 6.2 Hz, 2H), 4.89 (ABq, 2H), 3.90 (s, 3H); 13 C NMR (75 MHz, CDC13) (5 177.0, 156.3 , 156.0, 149.1, 142.5, 141.9, 138.9, 137.3, 131.9, 129.1, 129.0, 128.2, 124.5, 119.2, 118.5, 109.6, 103.0, 101.6, 93.7, 80.7, 58.5, 56.0; MS (ES+) m/z 389.3 ( M + 1). Example 2 1'-(Diphenylfluorenyl)-6-methoxy-5-mercaptospiro[1-benzopyran-3,3·_吲嗓]_2'(1·η )- Synthesis of ketone

Under nitrogen, 1-(diphenylmethyl)-3-(2-pyridyl-4-decyloxy-5-methylphenyl)-1,3-dihydro-2Η-吲哚-2- A mixture of ketone (10.6 g, 24.4 mmol) and cesium carbonate (23 g, 73.1 mmol) in tetrahydrofuran (100 mL). The mixture was allowed to mix at ambient temperature for 3 hours, then filtered through a solution of sulphur, and washed with tetrahydrotetramine (5 liters). The filtrate was concentrated in vacuo to dryness. The residue was recrystallized from diethyl ether (2 mL) to give Γ-(diphenylhydrazinyl)-6-decyloxy-5-methyl snail [ι_benzopyrene-3,3'-θ ]]-2'(1Ή)-one (7.9 g, 72%) as a colorless solid: 1h NMR (300 MHz, CDC13) 5 7.41-7.27 (m, 10H), 7.15 (dd, J = 7.1, 1.5 Hz , 1H), 7.07 (s, 1H), 7.05-6.92 (m, 2H), 6.55-6.49 (m, 2H), 6.34 (s, 1H), 4.86 (ABq, 2H), 3.80 (s, 3H), 2.01 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.1, 160.2, 159.2, 141.8, 137.8, 137.4, 132.9, 128.70, 128.66, 128.48, 128.46, 128.2, 128.0, 127.9, 124.2, 123.8, 123.1, 119.6, 112.2, 93.8, 80.4, 58.7, 57.7, 55.6, 16.1; 143924-sp-20091127-2 -340- 201020257 MS (ES+) m/z 448.3 (M + 1) 〇Example 2.1 4'-Chloro-1 '-(Diphenylfluorenyl)_5,6-dihydrospiro [benzoan is seven:5,4,7], two scent,

Refer to the procedure as described in Example 2 and perform an insignificant change using a winter gas-based [mercaptomethyl)m-carbyl-2,3-dihydrobenzophenanthrene-5-yl)- f -2Η,哚_2_ketone is substituted for quinonezyl)-3-(2-hydroxy-4-methoxymethylphenyl)-U-:hydrogenate_2_嗣, which gives *chloro group ]. Renqi methyl)_ 5,6-monohydrospiro [stupid and tl, 2_b: 5,4_b'] dim m (9) noise] but (%), colorless solid: MS (ES+) m/z 479.9 (Μ + 1), 481.9 (Μ + 1). Example 2.2 6-/Smellyl-1 -(monophenylmethyl)spiro[μbenzofuran-3,3, Qiao]_2, (ιΉ) ketone 03⁄4 in 3-(4-bromo-2-_2 Hydroxyphenyl) small (diphenyl fluorenyl) u dihydro 2 Η 吲哚 2 ketone (10.1 g, 22.6 mmol) with carbonic acid planer (221 g, 67.8 mmol) in tetrahydrofuran ( A gas base (5 88 g, 33.9 mmol) was added to the mixed solution in 100.0 ml). The mixture was stirred at ambient temperature for 3 hours and then filtered through a pad of silica gel, then rinsed with THF (500.0 mL). 143924-sp-20091127-2 -341 - 201020257 The filtrate was concentrated in vacuo to dry wine and recrystallized from diethyl ether (20.0 mL) in a water bath on a Branson ultrasonic bench to give 6-bromo- Γ-(diphenylfluorenyl)spiro[1-benzofuran-3,3·-indole]-2,(1Ή)-one (7.3 g, 67%) as colorless solid: iHNMRGOOMHtCDCls) δ 7.44-7.25 (m, 10H), 7.15-7.09 (m, 2H), 7.07-6.90 (m, 4H), 6.56-6.49 (m, 2H), 5.03 (d, J = 9.1 Hz, 1H), 4.76 (d, J = 9.1 Hz, 1H); MS (ES+) m/z 482.1 (M + 1), 484.0 (M + 1). Example 2.3 Synthesis of (i'h)-ketone by Γ-(diphenylfluorenyl)-5,6-dimethylspiro[l-benzopyran-3,3'·吲嗓]_2

1-(Diphenylfluorenyl)-3-hydroxy-3-(2-hydroxy-4,5-dimercaptophenyl)-1 was used according to the procedure as described in Example 2, and the insignificant change was applied. , 3-dihydro-2H-M丨哚-2-one substituted 1-(dimethylene)-3-(2-hydroxy-4-methoxy-5-fluorenylphenyl)-1,3- Dihydro-2H-indol-2-one, Γ-(diphenylmethyl)_5,6-diindolyl snail [μ benzopyran-3,3'-M bud]-2' (1Ή )-_ (54%), as a colorless solid: refining point 193-195 _. (:(ethyl acetate/hexane); NMR (300 MHz, CDC13) (5 7.38-7.32 (m, 10H), 7.14-6.92 (m, 4H), 6.75-6.78 (m, 1H), 6.55-6.50 (m, 1H), 6.37-6.31 (m, 1H), 4.99-4.94 (m, 1H), 4.73-4.65 (m, 1H), 2.20 (s, 3H), 2.05 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.9, 159.0, 141.7, 138.4, 137.7, 137.4, 132.8, 129.4, 128.6, 128.4, 128.1, 127.9, 127.8, 126.3, 123.8, 123.0, 112.2, 111.4, 79.7, 58.7, 57.8, 20.3,19.3; MS (ES+) m/z 432.3 (M + 1). Example 2.4 143924-sp-20091127-2 -342- (s) 201020257 (monophenylmethyl)-5'-fluoro-5,6 -Synthesis of dihydrospiro[benzofl,2_b : 5,4_b,]difuran_3,3,_* 啕哚]-2'(1Ή)-_

According to the procedure as described in Example 2, and irrelevant changes were made, 1-(diphenylmethyl)-5-fluoroyl (6-hydroxy-2,3 dihydrobenzobenzofuran-5 base) was used. 1,3-Dihydro-2Η-吲哚_2-one substituted Μ 苯 苯 ) 各 ( 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Γ((), Γ(())) ...color solid. Melting point 228-229 ° C (ethyl acetate / hexane); ι (3 〇〇 MHz, CDC13) (5 7.39-7.25 (m, 1 〇Η), 7.06 (s, 1H), 6.90- 6.87 (m, 1H), 6.72-6.65 (m, 1H), 6.42-6.38 (m, 3H), 4.83 (ABq, 2H), 4.53 (t, J = 9.0 Hz, 2H), 3.02-2.97 (m, 2H) ; MS (ES+) m/z 464.1 (M + 1). Example 2.5 Synthesis of bromine-2'(1Ή)-ketone

Xin 1'-(diphenylmethyl)-6'-fluoro-5,6-dihydrospiro[benzo[u_b:5,4_b,] two bite _3,3,_ as in Example 2 The procedure described, and the implementation of the insignificant change, using 1-(diphenylfluorenyl)-6-fluoroyl_3_(6-hydroxy-2,3 dihydrobenzobenzofuran_5_yl)_ U- Hydrogen-2Η-射-2-one replacement! Benzoquinone illusion _3 (2_carbyl _4 methoxy-m-methylphenyl)-1,3-dihydro-2H-吲哚_2, obtained! , benzoquinone&gt;6, gas radical 143924-sp-20091127-2 -343 - 201020257 -5,6-dihydrospiro[benzo[i,2-b: 5,4-b.]difuran- 3,3'-啕哚]-2'(ΓΗ)-ketone (87%), as colorless solid: mp 194-196 ° C (decyl alcohol); 1 NMR (300 ΜΗζ, CDC13) (5 7.42-7.25 ( m, 10H), 7.10-7.04 (m, 2H), 6.67-6.61 (m, 1H), 6.40-6.39 (m, 2H), 6.23-6.19 (m, 1H), 4.81 (ABq, 2H), 4.53 ( t, J = 9.0 Hz, 2H), 2.99 (t, J = 9.0 Hz, 2H); MS (ES+) m/z 463.8 (M + 1). Example 2.6 P-(4-Methoxybenzyl)- Synthesis of 3-mercaptospiro[吱,[3,2-f][l,2]benzisoxazole-5,3,-吲哚]-2'(ΓΗ)-one

3-(6-Hydroxy-3-methyl-1,2-benzisoxazole-5-yl)-1-(4-) was used according to the procedure as described in Example 2, and the insignificant change was applied. Replacement of 1-(diphenylindolyl)-3-(2-hydroxy-4-oximeoxy-5-methyl) with methoxybenzyl)-1,3-dihydro-2-indole-2-one Phenyl)-1,3-dihydro-2Η-indol-2-one, Γ-(4-methoxybenzyl)-3-indolyl snail [吱,[3,2-f] [l,2] Benzoisoxazole-5,3,-吲哚]-2,(ΓΗ)-one (95%), as colorless solid: mp 138-139 ° C (ethyl acetate /hexane) Old NMR (300 MHz, CDC13) &lt;5 7.46 (d, J = 9.0 Hz, 2H), 7.35 (d, J = 9.0 Hz, 2H), 7.21-7.18 (m, 1H), 7.11-7.09 (m , 1H), 6.96 (d, J = 9.0 Hz, 1H), 6.94-6.88 (m, 2H), 6.79 (d, J = 9.0 Hz, 1H), 5.16-4.79 (m, 4H), 3.78 (s, 3H), 2.45 (s, 3H); MS (ES+) m/z 412.9 (M+ 1) ° Example 2.7 Γ-Diphenylmethyl-6-(yloxy)-2H-spiro[benzofuran-3, 3,-Dihydroanthracene-2,-ketone 143924-sp.20091127-2 •344- 201020257

Under argon, benzyloxy)-2-hydroxyphenyl]succinic (diphenyl)-l,3-dihydro-2H-?-f-butanone (7·4 g ' 14·8 mM Mol), chloroiododecane (2.7 ml, phantom) in a stirred solution of anhydrous tetrahydrofuran (2 mL), φ 鏠 carbonate (15 &gt; 4 g, 47.4 mmol) ear). The mixture was stirred at ambient temperature for 16 hours and then filtered through a pad of Celite. The filtrate was concentrated under vacuum. The residue was purified by column chromatography (ethyl acetate / hexanes, 1/5), and then ethyl ether /hexanes to afford toluene, And furan-3,3-hydroquinone] 2'-one (4.1 g, 55%)' is a colorless solid: 11^1^(300 MHz, CDC13) δ 7.42-7.25 (m, 15H), 7.16- 7.09 (m, 1H), 7.07-6.90 (m, 3H), 6.62-6.38 (m, 4H), 5.03-4.90 (m, 3H), 4.73 (d, J = 9.0 Hz, 1H) ; MS (ES+) m/z 510.1 (M + 1) 〇 Example 2.8 1 -(Diphenylfluorenyl)-5-fluoro-6-methoxyoxyspiro[1-benzofuran-3,3,_吲哚]_2' ( I'h)- Synthesis of ketone

Following the procedure as described in Example 2, and carrying out irrelevant changes, 1-(diphenylmethyl)-3-(5-fluoro-2-hydroxy-4-methoxyphenyl)-indole, 3 ·Dihydro-2H- 143924-sp-20091127-2 -345- 201020257 Indole-2-one substituted 1-(diphenylmethyl)_3_(2-hydroxy-4-indolyl_5-methylphenyl ) _ 1,3-dihydro-2H-indol-2-one 'obtained Γ_(diphenyl fluorenyl) 5 - fluoroyl fluorenyl snail [1-bens pfu 0 south-3,3-啕ρ朵]-2'(1Ή)-嗣(73%), as a colorless solid: 1h NMR (300 MHz, CDC13) δ 7.43-7.22 (m, 10H), 7.16-7.09 (m, 1H), 7.06- 6.92 (m, 3H), 6.60 (d, J = 6.8 Hz, 1H), 6.54-6.48 (m, 1H), 6.37 (d, J = 10.0 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H ), 4.72 (d, J = 9.0 Hz, 1H), 3.85 (s, 3H); MS (ES+) m/z 452.1 (M + 1). Example 2.9 Γ-(diphenylmethyl)-5-carbyl Snail [1-benzofuran-3,3,_吲哚]_2, (1Ή)-ketone

According to the procedure as described in Example 2, and irrelevant changes were made, 1-(diphenylmethyl)-3-(5-fluoro-2-hydroxyphenyl)-1,3-dihydro-2Η was used. -Indol-2-one substituted 1-(diphenylmethyl)-3-(2-hydroxy-4-decyloxy-5-mercaptophenyl)-1,3-dihydro-2Η-吲嗓- 2-ketone' obtained Γ-(diphenylhydrazinyl)-5-gasylspiro[μbenzofuran_3 3,_ 哚 哚]-2'(1Ή)-one (56%) as a colorless solid: melting point 182 -184. (: ; 1H NMR (300 ® MHz, CDCI3) δ 7.43-7.25 (m, 10H), 7.17-7.10 (m, 1H), 7.07-6.84 (m, 5H), 6.56-6.49 (m, 1H), 6.39 -6.32 (m, 1H), 5.01 (t, J = 9.0 Hz, 2H), 4.74 (t, J = 9.0 Hz, 2H); 13 C NMR (75 MHz, CDC13) δ 177.0, 159.3, 156.8, 156.1, 141.7, 137.5, 137.2, 131.9, 130.3, 130.2, 128.8, 128.7, 128.6, 128.4, 128.3, 128.1, 127.9, 123.8, 123.3, 116.5, 116.1, 112.4, 110.9, 110.8, 110.6, 110.2, 80.3, 58.8, 58.0; MS (ES+) m/z 444.0 (M + 23). Example 2.10 143924-sp-20091127-2 •346- (S) 201020257 '-(Diphenylfluorenyl)-6-methoxyspiro-u-benzofuran _3,3,吲哚]_2,(1Ή)_ketone synthesis

According to the procedure as described in Example 2, and irrelevant changes were made, using i-(diphenylmethyl)_3_(2, hydroxy-4 methoxyphenyl hydrazine, 3 dihydro 2 Η峋哚 2 ketone Displacement of 1-(diphenylfluorenyl)-3-(2-hydroxy-4-cyclomethoxy-5-mercaptophenyl)-indole, 3-dihydro-2Η-indol-2-one, to obtain Γ_( Diphenylmethyl)_6-methoxy oxobenzofuran _3,3,_ _ 十来]·2'(1Ή)·_ (74%), as a colorless solid: 4 NMR (300 MHz, CDC13) δ 7.42-7.27 (m, 10H), 7.16-6.92 (m, 4H), 6.59-6.49 (m, 3H), 6.37 (dd, J = 8.4, 2.4 Hz, 1H), 5.02 (d, J = 9.0 Hz, 1H), 4.75 (d, J = 9.0 Hz, 1H), 3.77 (s, 3H) ' MS (ES+) m/z 434.3 (M + 1), 456.3 (M + 23). Example 2.11 (Diphenylmethyl) Synthesis of -2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxolene-8,3^吲哚]-2·(1Ή)-嗣

Follow the procedure as described in Example 2 and perform an insignificant change 'Using 1-(diphenylfluorenyl)_3_(7-hydroxy-2,3_dihydroyi^benzodioxene _6_ group H'3-Dihydro-2H-chatty-2-one substituted 1-(diphenylmethyl)_3_(2-hydroxylmethoxy-5-methylphenyl)-1,3-dihydro-2H -p5buxo-2-one, 1'-(diphenylmethyl)_2 3_dihydrospiro[w, methane[2,3-g][l,4]benzodioxolene _8 3 , _吲哚]_2, (1 but ketone 143924-sp-2009l 127-2 -347- 201020257 (68%), as colorless solid: melting point 183-185 ° C (methanol); 1H NMR (300 MHz, CDC13 δ 7.41-7.28 (m, 10Η), 7.15 (dd, J = 6.8, 1.4 Hz, 1H), 7.06 (s, 1H), 7.04-6.93 (m, 2H), 6.52-6.48 (m, 2H), 6.21 (s, 1H), 4.95 (d, J = 8.9 Hz, 1H), 4.69 (d, J.= 8.9 Hz, 1H), 4.22-4.17 (m, 2H), 4.15-4.10 (m, 2H); 13C NMR (75 MHz, CDCI3) δ 177.8, 155.3, 144.7, 141.8, 138.4, 137.7, 137.5, 132.6, 128.83, 128.75, 128.5, 128.44, 128.36, 128.02, 127.98, 123.9, 123.2, 121.5, 112.3, 111.6, 99.5 , 80.4, 64.6, 64.0, 58.8, 57.9; MS (ES+) m/z 462.3 (M + 1). Example 2.12 Γ-(diphenylmethyl)-6/ Synthesis of 7-dihydro-5H-spiro[吱,[3,2-g]nonene-3,3,-吲 哚]-2'(1Ή)-one

According to the procedure as described in Example 2, and irrelevant changes were made, 1-(diphenylmethyl)-3-(7-hydroxy-3,4-dihydro-2-indole-6-yl) was used. -1,3-Dihydro-2-indole-2-one substituted 1-(diphenylfluorenyl)_3_(2-hydroxy-4-yl-methoxy-5-nonylphenyl)-1,3-dihydrogen -2Η-'嗓-2-ketone' obtained ι·_(diphenylfluorenyl)_6,7 dihydro-5 Η snail [biting Nanhe [3,2-g] decene-3,3'-〃哚]_2,(1,Η)-one (70%), as an off-white solid: mp 208-211 C (hexane); 4 NMR (300 MHz, CDC13) (5 7.41-7.29 (m, 10H), 7.16 (dd, J = 6.6, 1.8 Hz, 1H), 7.08 (s, 1H), 7.05-6.94 (m, 2H), 6.52 (d, J = 7.8 Hz, 1H), 6.41 (s, 1H), 6.28 ( s, 1H), 4.96 (d, J = 9.0 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.11 (dd, J = 5.1, 5.1 Hz, 2H), 2.56 (t, J = 6.3 Hz, 2H), 143924-sp-20091127-2 -348- 201020257 1.94-1.86 (m, 2H) ; 13C NMR (75 MHz, CDC13) 5 178.1, 160.1, 156.3, 141.8, 137.9, 137.5, 132.9, 128.75, 128.73, 128.53, 128.52, 128.2, 128.00, 127.96, 132.9, 132.8, 123.2, 121.3, 115.2, 112.3, 98.9, 80.3, 66.6, 58,8, 57.5, 24.8, 22.3; MS (ES+) m/z 460.1 (M + 1). Example 2.13 Γ-(diphenylfluorenyl)-3,4-dihydro-2H-spiro[吱,[2,3-h][l,5]benzodiazepine seven Synthesis of ene-9,3W-b]2-(1Ή)-ketone

Following the procedure as described in Example 2, and applying an insignificant change, 1-(diphenylindenyl)-3-(8-carbyl-3,4-dihydro-2H-1,5-benzo -dioxynitridin-7-yl)-1,3-dihydro-2Η-Θ|p-butanone-substituted 1-(diphenylmethyl)-3-(2-yl)-4- Methyl 5-methyl-phenyl)-1,3-dihydro-2Η-indol-2-one, 1'-(diphenylindenyl)-3,4-dihydro-2H-spiro [吱吱[2,3-h][l,5]benzodioxanthene-9,3,-吲β 哚]-2'(1Ή)-one (75%), pale pink Color solid: 165-168 ° C (ethyl acetate / decyl alcohol); 1H NMR (300 MHz, CDC13) ί 7.42-7.28 (m, 10H), 7.15 (dd, J = 7.2, 1.4 Hz, 1H), 7.2 (s, 1H) , 1H), 4.71 (d, J = 9.0 Hz, 1H), 4.29-4.22 (m, 1H), 4.16-4.03 (m, 2H), 4.01-3.93 (m, 1H), 2.24-2.01 (m, 2H 13C NMR (75 MHz, CDC13) 5 177.7, 156.9, 153.1, 146.4, 141.8, 137.7, 137.6, 132.5, 128.9, 128.8, 128.6, 128.44, 128.41, 128.0, 124.0, 123.4, 123, 2, 116.1, 112.3 , 103.6, 80, 7, 70.92, 70.88, 58.8, 57.8, 32.3 ; MS (ES+) 143924-sp-20091127-2 •349· 201020257 m/z 476.1 (Μ + 1). Example 2.14 Synthesis of Γ-(diphenylmethyl)-2-methylspiro[吱,[2,3-f][i,3]benzoxazolium m 哚]-2'(1Ή)-one

According to the procedure as described in Example 2, and with irrelevant changes, 1-(diphenylmethyl)-3-(5-yl-2-methyl-1,3-benzo&lt;»坐, 坐, ❹, ❹, ❹, ❹ 酮 酮 1- 1- 1- 1- 1- 1- 1,3-Dihydro-2Η-indol-2-one, obtaining 1'-(diphenylmethyl)_2_indolyl snail [bito-and-[2,3-f][l,3] benzo ρ N-azole-7,3'-indole]-2'(1Ή)-one (68%) as colorless solid: m.p. 240-242°C (dioxane); 1H NMR (300 MHz, CDC13) 5 7.66 (d, J = 7.2 Hz, 2H), 7.45-7.29 (m, 9H), 7.11-6.97 (m, 4H), 6.89 (t, J = 7.2 Hz, 1H), 6.46 (d, J = 7.8 Hz , 1H), 6.01 (d, J = 5.7 Hz, 1H), 5.41 (d, J = 5.7 Hz, 1H), 2.47 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 175.1, 164.5, 151.3, 146.2, 143.7, 138.6, 138.0, 137.3, 129.9, 129.8, 129.0, 128.9, 128.8, 128.3, O 128.0, 127.7, 124.6, 122.8, 114.0, 112.7, 111.8, 110.7, 88.7, 75.8, 58.6, 14.8; MS (ES+ ) m/z 497.1 (M + 39). Example 2.15 Γ-(Diphenylmethyl)-1-methyl-1H-spiro [bito-and-[3,2-g][l,4]benzoindole -8,3', 哚]-2 , 2' (1's 3-print-dione synthesis 143924-sp-20091127-2 -350- (8) 201020257

'N CH3 Ph

Methoxy-5-fluorenyl) 4,3-dihydro-2H-indole-2-one, obtained, (diphenylhydrazinyl-methyl-1H-spiro[吱然[ from illusion Benzopyrene _ _8,3,10 幻_2,2,(1Ή, ❹3Η&gt;dione (32%), colorless solid: 4 NMR (300 ΜΗζ, dough bucket) 5 7.47-7.23 (m, 11H ), 7.19-7.10 (m, 1H), 7.07-6.98 (m, 1H), 6.88 (s, 1H), 6.72 (s, 1H), 6.64 (d, J = 7.9 Hz, 1H), 6.20 (s, 1H), 4.93 (d, J = 9.4 Hz, 1H), 4.82 (d, J - 9.4 Hz, 1H), 4.57 (s, 2H), 3.01 (s, 3H); MS (ES+) m/z 489.0 ( M + 1) ° Example 2.16 Γ-(Diphenylmethyl)-3_methylspiro[吱-benzobenzoxazole-7,3•-嘀哚]-2,2'(1凡3«〇- Diketone synthesis

According to the procedure as described in Example 2, and the insignificant change was made, 6-[1-(monobenzyl)-2-keto-2,3-dihydro-lH-p?bido-3 was used. -yl]-5-carbamic-3-methyl-1,3-benzoxazole-2 (3H&gt; ketone replacing 1-(diphenylmethyl)_3_(2-hydroxylmethoxy-5-methyl Phenyl)-1,3-dihydro-2H-indol-2-one, obtaining 1'-(diphenylindenyl)_3_methylspiro[吱,[2,3-:〇[1,3] Benzene -7,3·-吲p]-2,2·(1Ή,3Η)-dione (40%) 'is a colorless solid: melting point 228_229〇c (ethyl acetate); 1hnmr (3〇 〇 143924-sp-20091127-2 -351 - 201020257 MHz, CDC13) δ 7.42-7.28 (m, 10H), 7.15-6.96 (m, 4H), 6.60 (s, 1H), 6.55 (d, J = 7.2 Hz , 1H), 6.44 (s, 1H), 5.04 (d, J = 9.0 Hz, 1H), 4.77 (d, J = 9.0 Hz, 1H), 3.38 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 177.6, 157.7, 155.3, 142.0, 137.7, 137.4, 137.2, 133.2, 132.1, 129.0, 128.9, 128.6, 128.5, 128.3, 128.2, 124.0, 123.5, 122.6, 112.6, 105.4, 92.0, 80.6, 59.1, 58.0, 28.5 MS (ES+) m/z 475.1 (M + 1). Example 2.17 1L (diphenylhydrazinyl-fluorenyl snail [吱,[3,2-f][l,3] benzo, azole- 7,3 - indole] -2,2 | (1Η, 1Ή) - -dione The

= 〇 according to the procedure as described in Example 2, and performing an insignificant change, using 5-[1-(diphenylmethyl)_2-keto-2,3-dihydro-1H-indole-3- Replacement of 1-(diphenylmethylhydroxy-4-methoxy-5-nonylphenyl) with benzyl-3-yl-1,3-benzoxazole-2(3H)-one )-1,3-Dihydro-2H-indol-2-one, obtained Γ-(diphenylfluorenyl)-1-methyl snail [bite. Nanhe [3,2-f][l,3]benzoxazole-7,3,-〃 〃]-2,2'(1Η,1Ή)-dione (65%) ' is a colorless solid: iHNMR (3〇〇MHz, DMS〇_d6) occupies 7 47_728(m, 11H), 7.18-7.11 (m, 2H), 7.06-6.99 (m, 1H), 6.89 (s, 1H), 6.64 (d, J = 7.9 Hz, 1H), 6.45 (s, 1H), 4.92 (d, J = 9.4 Hz, 1H), 4.81 (d, J = 9.4 Hz, 1H), 3.18 (s, 3H) ; MS (ES+) m/z 475.0 (M + 1). Example 2.18 7'-Gasyl-1'-(diphenylmethyl)_5,6-dihydrospiro[benzo[12_b:5,4 b,]difuran_3 3,·β哚]-2χΐΉ)- Synthesis of ketones 143924-sp-20091127-2 -352- 201020257

According to the procedure as described in Example 2, and with irrelevant changes, use 7-alkyl-indolyl hydrazinyl) 3 (b-yl-2,3-dichlorobenzophenone and determine the base)_U-gas -2H-巧嗓_2_纲换 μ(diphenylfluorenyl) 3 "2_hydroxy_4_decyloxy_5_methylphenyl)-1'3-dihydro-2Η-fluorenone, obtained 7'_Chloro],-(diphenylmethyl)_ 5,6-a snail [benzo[12:5:5,7,7,5,4,3,10]], (ιή)嗣(秘), ❿ is a colorless solid. lH NMR (3 〇〇 MHz, DMSO-d6) 3 7.45-7.06 (m, 14H), 6.38-6.32 (m, 2H), 4.75 (s, 2H), 4.48 (t, J = 8.7 Hz, 2H), 2.94 (t, J = 8.7 Hz, 2H) 〇 Example 2.19 (monophenylmethyl M'-fluoro-7'-fluorenyl_5,6-dihydrospiro[benzo[nb:5] , 4 b,] Synthesis of difuran-3,3'-啕哚]-2, (l,H)-_

According to the procedure as described in Example 2, and with irrelevant changes, 1-(diphenylmethyl)-7-fluoro-based 3-(6-hydroxy-2,3-dihydro-1-benzofuran- 5-yl)-1,3-dihydro-2H-indol-2-one substituted 1_(diphenylfluorenyl) each (2-hydroxypipemethoxy_5_methylphenyl)-1,3-di Hydrogen-2H-W哚-2-one, 1'-(diphenylmethyl)_4,·fluoroyl-7--fluorenyl-5,6-dihydrospiro[benzo-like seven:5,4-7 ,]difuran-3,3,-anthracene-2,(1Ή)-one (89%) 'as colorless solid: melting point 81_82〇c (hexane/ethyl acetate); lHNMR (300 MHz, DMSO- c^) δ 7.44-7.23 (m, 10Η), 7.18-7.22 (m, 1H), 6.94 (br s, 143924-sp-20091127-2 •353 · 201020257 1H), 6.85-6.78 (m, 1H), 6.45 (s, 1H), 6.33 (s, 1H), 4.83 (d, J = 9.5 Hz, 1H), 4.69 (d, J = 9.5 Hz, 1H), 4.52-4.50 (m, 2H), 3.08-2.86 (m, 2H), 2.33 (br s, 3H) ; m/z 477.9 (M+l). Example 2.20 1 -(a sulphonyl)-7'-fluoro-5,6-dihydrospiro[benzo[[7:5,4,7]]difuran_3,3,_ 吲哚]-2 Synthesis of '(1'H)-嗣

According to the procedure as described in Example 2, and with irrelevant changes, 7-fluoro-1-(diphenylmethyl)_3_(6-hydroxy-2,3-dihydrobenzobenzofuran-5 base was used. )_1'3-dihydro-2H-W嗓-2-one substituted 1_(diphenylmethyl)_3_(2_hydroxy_4_methoxy_5_nonylphenyl)-1,3-dihydrogen -2H-indol-2-one, Γ-(diphenylmethyl)_7*-fluoro-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran- 3,3,- 哚 哚]-2, (1,; «)-ketone (70%), as a colorless solid: mp 183-184. (:(hexane/ethyl acetate); old NMR (300 MHz, DMSO-d6) δ 7.45-7.22 (m, 10H), 7.13-7.05 (m, 3H), 6.98 (s, 1H), 6.44-6.43 (m, 2H), 4.91 (d, J = 9.5 Hz, 1H), 4.80 (d, J = 9.5 Hz, 1H), 4.51 (t, J © =8.9 Hz, 2H), 2.97 (t, J = 8.6 Hz, 2H); MS (ES+) m/z 463.9 (M + 1). Example 2.21 6-(----------------------- , the synthesis of ketone

143924-sp-20091127-2 .354 (S) 201020257 According to the procedure as described in Example 2, and with irrelevant changes, use 3-[4-(indicyl)_2_hydroxyphenyl] small (3 _mercaptobutyl)_13 dihydro 2H 哚 哚 嗣 嗣 嗣 1- 1- 1-(diphenylfluorenyl)·3_(2_hydroxy_4 methoxy_5_methylphenyl)_13-dihydro- 2Η-Planta-2-ketone' obtained 6_(benzyloxyindole, _(3_mercaptobutyl)spiro[]L_benzofuran-3,3 -10]-2' (1,H&gt; Ketone (67%): 1H NMR (300 MHz, CDC13) (5 7.41-7.28 (m, 7H), 7.14-7.12 (m, 1H), 7.04-6.99 (m, 1H), 6.90-6.87 (m, 1H ), 6.59-6.55 (m, 1H), 6.44-6.30 (m, 1H), 5.00 (s, 2H), 4.79 (ABq, 2H), 3.87-3.64 (m, 2H), 1.71-1.56 (m, 3H) ), 0.98 (d, J = 6.0 Hz, 6H); MS (ES+) m/z 414.3 (M + 1). Example 2.22 6-Mosyl-1'-((5-(Trifluoromethyl) Synthesis of _2_yl)methyl snail [benzofuran_3,3,_dihydroanthracene] ketone

3- 3-(4-Molyl-2-hydroxyphenyl)-1_((5-(trifluoromethyl)pyran-2-yl) was used according to the procedure described in Example 2, and irrelevant changes were applied. ) fluorenyl) indan-2-one substituted 1-(diphenylmethyl) each (2-hydroxyindoleoxy_5_methylphenyl)_1,3-dihydro-2H-indole 2-ketone, 6-bromo 1-((5-(trifluoromethyl)-propan-2-yl)methyl)-2H-spiro[benzofuran_3,3·-dihydroindole ]-2,-ketone (78%) as colorless solid: 4 NMR (300 MHz, CDC13) &lt;5 7.30 (ddd, J = 7.9, 7.9, 1.5 Hz, 1H), 7.16-7.03 (m, 3H) , 6.69 (d, J = 7.9 Hz, 1H), 6.93 (dd, J = 8.2, 1.8 Hz, 1H), 6.77-6.71 (m, 1H), 6.53 (d, J = 8.2 Hz, 1H), 6.42- 6.37 (m, 1H), 5.06 (d, J = 16.1 Hz, 1H)S 4.97 (d, J = 9.4 Hz, 1H), 4.86 (d, J = 16.1 Hz, 1H), 4.71 (d, J = 143924 -sp-20091127-2 -355 - 201020257 9.4 Hz, 1H) ; 13C NMR (75 MHz, CDC13) δ 176.5, 161.5, 151.8, 141.4, 131.6, 129.3, 128.0, 124.5 (6), 124.0, 114.2, 112.6 (6), 109.2 (6), 80.1, 57.5, 36.9; MS (ES+) m/z 463.9 (Μ + 1), 465.9 (Μ + 1). Example 2.23 5-Bromo-1:((5-(Trifluoromethyl)decan-2-yl)methyl)-2Η-spiro[benzofuran-3,3'-dihydroanthracene-2 '-ketone synthesis

According to the procedure as described in Example 2, and with irrelevant changes, 3-(5-bromo-2-hydroxyphenyl)-1-((5-(trifluoromethyl)pyran-2-) was used. (indenyl) indenyl-2-one substituted 1-(diphenylfluorenyl)_3_(2_hydroxyindoleoxy_5_mercaptophenyl)_1,3-dihydro-2HH2-ketone 'Get 5-bromo-1,-((5.(trifluoromethyl)furan-2-yl)methyl)-2Η-spiro[benzofuran_3,3'-dihydroanthracene]·2 '_ketone (78%) as a colorless solid. 1H NMR (300 MHz, CDC13) &lt;5 7.36-7.27 (m, 2 Η), 7.17-6.98 (m, 3 Η), 6.8 (d, J = 8.6 Hz, 1H), 6.78-6.72 (m, 2H), 6.39 (d, J = 3.4 Hz, 1H), 5.07-5.87 (m, 3H), 4.69 (d, J = 9.1 Hz, 1H) ; MS (ES+) m /z 463.9 (M + 1), 465.9 (M + 1). Example 2.24 6·-Isoamyl-3'7-dihydro-2H-spiro[benzofurodioxanthene-8,8--pyrazolo[5,4-caffe]-7, Synthesis of (6Ή)-ketone 143924-sp-20091127-2 •356· 201020257

8-(7-Hydroxy-2'3-dihydrobenzo[b][1,4]dioxene base)_6 was used according to the procedure as described in Example 2, and irrelevant changes were applied. Isoamyl-6H-thiazolo[5,4-e]indole-7(8H)-one is substituted for l(diphenylmethyl)3 (2hydroxy-4-yloxy-5-nonylphenyl) Hydrogen 2H吲哚_2-ketone, 6 is obtained, isoamyl φ dihydro-2H_spiro [benzofuro[5,6-b][l,4]dioxopinene-8,8, _thiazolo[5'4-φ5丨嗓]-7·(6Ή)-one (17%) as colorless solid: mp 169·17 Γ (:; NMR (300 MHz, CDC13) ^ 8.89 (s, 1H ), 8.18 (d, J = 8.5 Hz, 1H), 7.19 (d, J = 8.5 Hz, 1H), 6.59 (s, 1H), 6.21 (s, 1H), 4.84 (ABq, 2H), 4.30-4.17 (m, 2H), 4.17-4.08 (m, 2H), 4.03-3.89 (m, 1H), 3.90-3.75 (m, 1H), 1.91-1.51 (m, 3H), 1.04 (d, J = 6.1 Hz , 6H) ; MS (ES+) m/z 423.1 (M + 1). Example 2.25 6-((5-(trimethyl)c-cyl)methyl)_2,3,5,,6,_ Tetrahydro-2 snail [4,4]dioxanthene [2,3-fH丨哚-8,3'-benzopyrano[6,5-b] acetyl]-7(6Η) -ketone synthesis

According to the procedure as described in Example 2, and irrelevant changes were made, 8-(6-trans- 2,3-dihydrobenzofuran-5-yl) each ((5-(trifluoromethyl)) was used.吱 _2 _ _ _ _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 _2 [ [ [ [ [ [ [ 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 Each) (2-hydroxy 4-methoxy-5-methylphenyl)-indole, 3-dihydro-2Η-143924-sp-20091127-2 -357· 201020257 吲哚-2-one, obtained 6 -((5-(Trifluoromethyl)pyran-2-yl)indolyl)-2,3,5,,6--tetrahydro-2Ή-spiro[[1,4]dioxanthene [2,3-f]11?Budu-8,3'-Benzo-p-dea-[6,5-b]-methane]-7(6H)-one (42%), as colorless solid: melting point 189-191°C; WNMRGOO MHz, CDC13) δ 6.77-6.73 (m, 1Η), 6.72 (s, 1H), 6.52-6.45 (m, 2H), 6.43-6.36 (m, 2H), 4.91 (ABq, 2H), 4.77 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H), 4.27-4.14 (m, 4H), 3.10-2.90 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 177.6, 161.8, 161.0, 151.9, 143.9, 140.1, 135.2, 124.9, 120.2, 120.0, 118.8, 113.6, 112.6 (d, J = 2.8 Hz, 1C), 109.2, 98.8, 93.1, 80.4, 72.4, 64.6, 64.0, 57.5, 37.0, 28.9 ; MS (ES+) m/z 485.9 (M + 1). Example 2.26 6-(((R)-E9-hydrofuran-2-yl)methyl)-2,3,5,6,-tetrahydro-2 ugly-spiro[[1,4]dioxene Synthesis of [2,3-f]吲哚-8,3^benzofuro[6,5-b]furan]-7(6H)-one

According to the procedure as described in Example 2, and with an insignificant change, 8-(6-carbyl-2,3-dihydrobenzofuran-5-yl)-6-((())- Tetrahydrofuran-2-yl)methyl)-6,8-dihydro-2H-[1,4]dioxolynene[2,3-fH哚-7(3H)-one substituted 1- (Diphenylmethyl)-3-(2-hydroxy-4-methoxy-5-methylphenyl)_i,3-dihydro-2H-indol-2-one, obtaining 6-(((R )-cghydrofuran_2_yl)indenyl)_2,3,5,6,_tetrahydro-2-indole-spiro[[1,4]dioxoisenene[2,3-fH丨哚_ 8,3 l of benzofuro[6,5-b]furan]-7(6H)-one (39%) as a colorless solid: m.p. (: ; 1H NMR (300 MHz, CDCI3) δ 6.65 (s, 1Η), 6.64-6.60 (m, 1H), 6.51-6.46 (m, 1H), 6.36 (s, 1H), 4.72 (dd, J = 84.4, 8.9 Hz, 2H), 4.51 (dd, J = 8.6, 8.6 Hz, 2H), 4.25-4.19 (m, 143924-sp-20091127-2 - 358 - 201020257 2H), 4.19-4.13 (m, 2H) , 3.94-3.82 (m, 2H), 3.80-3.67 (m, 2H), 3.64-3.52 (m, 1H), 2.98 (t, J = 8.6 Hz, 2H), 2.08-1.94 (m, 1H), 1.94 -1.80 (m, 2H), 1.74-1.60 (m, 1H); MS (ES+) m/z 421.9 (M + 1). Example 2.27 6-((5-(tri-l-methyl) oxime. -yl) fluorenyl)-2,3,3',7,-tetrahydro-2-indole-spiro[[1,4]dioxolysine [2,3-fH丨哚-8,8·- stupid Synthesis of furo[5,6-b][l,4]dioxanthene]-7(6H)-one

Using 8-(7-hydroxy-2,3-dihydrobenzo[b][l,4]dioxolene-6-yl, according to the procedure described in Example 2, and insignificantly changing -6-((5-(Trifluoromethyl)furan-2-yl)methyl)-6,8-dihydro-2H-[1,4]dioxo-enoxane[2,3-f啕哚-7(3H)-keto-substituted 1-(diphenylmethyl)-3-(2-pyridyl-4-methoxy-5-methylphenyl)-1,3-dihydroanzepine -2-ketone's 6-((5-(trifluoromethyl)-anthran-2-yl) fluorenyl)-2,3,3·,7--tetrahydro-2Ή-spiro[[1, 4] Dioxetene-[2,3-fH哚-8,8·-benzofuro[5,6-b][l,4]dioxolene]-7(6Η)-_ (76%) as colorless solid: mp 176-178 ° C; 4 NMR (300 MHz, CDC13) 6 6.75-6.67 (m, 2 Η), 6.49-6.43 (m, 2H), 6.37-6.31 (m, 1H ), 6.22-6.16 (m, 1H), 4.87 (ABq, 2H), 4.69 (ABq, 2H), 4.26-4.04 (m, 8H); 13 C NMR (75 MHz, CDC13) δ ΠΊ2, 155.0, 152.0, 151.9, 144.6, 144.0, 140.1, 138.3, 135.2, 124.3, 120.9, 113.7, 112.6, 112.6, 111.5, 109.1, 99.3, 98.9, 80.0, 64.6, 64.5, 64.0, 63.9, 57.8, 37.0; MS (ES+) m/ z 501.9 (M + 1). 143924-sp-20091127-2 -359- 201020257 Example 2.28 1-Mercapto-indole-{[5-(trifluoromethyl)-propan-2-yl]methyl b 2,3-dihydro-m spiro &amp; Synthesis of Fudan[3,2-g][l,4]benzoxanthene_8,3,_吲哚]_2ι(ιή)-ketohydrochloride

According to the procedure as described in Example 2, and irrelevant changes were made, 3-(7-pyridylmethyl-3,4-dihydro-2Η-1,4-benzoindole was used)_Η [5-(Trifluoromethyl)furan-2-yl]methyl}-indole, 3-dihydro-2Η-indol-2-one trifluoroacetate substituted 1-(diphenylfluorenyl)&gt;3_(2 _Hydroxyindoleoxy_5_methylphenyl)udihydro-2-indole_bumu-2-one 'obtained ι_methylfluoroindolyl) puffan-2-yl]methyl b 2,3_ dihydrogen -1Η-Snail [吱 并[3,2_g][1,4]Benzene 哼 ··8,3,_吲哚] (1) ketone. 1-mercapto-indole-{[5-(trifluoromethyl)pyran-2-yl]indenyl}_2,3-dihydro-1indole-spiro[snolo[3,2-g][ l, 4] benzopyrene _8,3'-吲哚]_2, (1,H)-one (0.59 g, 1.3 mmol) in a suspension in decyl alcohol (8.5 ml), add ι Hydrochloric acid (1.5 ml, 6.0 mmol) in 4D dioxane, and the resulting solution was stirred at ambient temperature for 35 minutes. The solvent was removed and the residue was dried under reduced pressure. Then, the residue was precipitated by adding hexane, sonicated, and the solvent was removed under reduced pressure. This method was repeated several times ' until the solid formed a fine suspension in the hexane. Next, the material was collected by hydrazine and air-dried to give methyl(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydro-1H-spiro[furo[3,2 -g][l,4]benzopyranin-8,3'-吲哚]-2'(1Ή)-one hydrochloride (〇.6〇, 94%), light gray powder: melting point 105 ° C (decomposition) (hexane); 1 H NMR (300 MHz, DMSO-d6) 5 7.33 143924-sp-20091127-2 • 360- 201020257 (ddd, J = 7.8, 7.5, 0.9 Hz, 1H), 7.22-7.17 (m, 3H), 7.07 (dd, J = 7.5, 7.5 Hz, 1H), 6.74 (d, J = 3.3 Hz, 1H), 6.48 (s, 1H), 6.25-6.19 (m, 1H) , 5.10 (d, J = 16.2 Hz, 1H), 5.02 (d, J = 16.2 Hz, 1H), 4.76 (d, J = 9.3 Hz, 1H), 4.65 (d, J = 9.3 Hz, 1H), 4.33 -4.22 (m, 2H), 3.27-3.18 (m, 2H), 2.68 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6) δ 176.4, 157.2, 153.2, 147.9, 141.9, 139.6 (q, J = 42.0

Hz), 131.3, 129.0, 123.9, 123.4, 121.5, 119.0 (q, J = 267 Hz), 114.2 (q, J = 2.8 Hz), 112.4, 109.9, 109.3, 98.8, 79.9, 62.7, 57.1, 48.8, 48.6 , 41.5, 36.6 ; MS (ES+) m/z 457.1 (M + 1); (: 24: 9FN204 · HC1: C, + 58.49; H, 4.09; N, 5.68; Found: C , 58.85; H, 3.74; N, 5.37. Example 2.29 1-Methyl-l'-[(2R),hydrofuran-2-ylmethyl]-2,3-dihydro-1H-spiro[puffan Synthesis of [3,2-layer][1,4]benzoxamicin-8,3'-吲哚]-2'(1,11)-ketohydrochloride

According to the procedure as described in Example 2, and irrelevant changes were made, using 3-(7-hydroxy-4-indolyl-3,4-dihydro-2H-1,4-benzoic -6- -l-[(2R)-tetrahydrop-pentan-2-ylmethyl]-1,3-dihydro-2H-P?丨, oxime-2-trifluoroacetate replacement 1-(two Benzyl)-3-(2-hydroxy-4-decyloxy-5-fluorenylphenyl H,3-dihydroindol-2-one, 1-ylidene-1,-[(2 tetrahydrofuran) _2_ylmethyl]_2,3_dihydro_1Η· sulphide[3,2-g][l,4]benzoindole-8,3'-吲哚]-2,( 1 Ή)-ketone (72%) as a colorless solid. 1-methyl-1'-[(211)-tetrahydrofuran-2-ylmethyl was used according to the procedure described in Example 2.28, and the insignificant change was applied. ]_2,3_Dihydro-1Η-spiro[吱,[3,2-g][l,4]Benzene -8,3'-峋哚]-2,(1Ή)-one substitution 1-曱基143924-sp-20091127-2 •361 - 201020257 {[5-(Trifluoromethyl)pyran-2-yl]methyl}-2,3-dihydro-1H-spiro[吱[3,2-g] [1,4]benzoindole-8,3M丨哚]-2'(1Ή)-one, 1-methyl-l'-[(2R)-tetrazolidine- 2-ylindenyl]-2,3-dihydro-1H-spiro [bito-and-[3,2-g][l,4]benzin-8, 吲哚]-2'(1Ή) -ketone salt Salt (83%) as colorless solid: m.p. &lt; 135 ° C (decomposition) (hexanes); 1H NMR (300 MHz, DMSO-de) (diastereomers) (5 7.83 (br s, 1H) ), 7.36-7.29 (m, 1H), 7.22 (d, J = 8.1 Hz, 1H), 7.15 (d, J = 7.5 Hz, 1H), 7.07-7.00 (m, 1H), 6.51 (br s, 1H ), 6.44, 6.40 (br s, 1H), 4.82-4.59 (m, 2H), 4.38-4.26 (m, 2H), 4.25-4.14 (m, 1H), 3.87-3.69 (m, 3H), 3.66- 3.59 (m, 1H), 3.36-3.24 (m, 2H), 2.78, 2.75 (br s, 3H), 2.02-1.72 (m, 3H), 1.68-1.55 (m, 1H) ; 13 C NMR (75 MHz , DMSO-dg) (diastereomers) 6 176.8, 158.2, 157.8, 148.3, 143.1, 142.9, 131.5, 131.2, 128.9, 128.8, 123.6, 123.5, 122.9, 122.3, 114.0, 113.3, 109.9, 109.8, 98.9, 79.9, 79.8, 75.7, 75.6, 67.3, 62.3, 57.0, 48.9, 43.9, 43.7, 42.3, 42.1, 28.7, 28.5, 25.2, 25.1; MS (ES+) m/z 393.1 (M + 1). Example 2.30 4-decyl-l'-[(2R)-rahydrofuran·2_ylindenyl]_3,4_dihydro-ban_snail [吱,[2,3-g][l,4 Benzene plowing _8,3,_吲哚]_2, (1Ή)嗣, the synthesis of CH,

According to the procedure as in Example 2, ih, 々β &gt;, and the insignificant change is performed using 3-(6-base--4-a very L q / 甲甲暴·3,4~二Wind-2H-M-benzopyrene _7_yl)-i-[(2R)_hydrogenate-2-ylmercaptoι_ι 3 Λ ,H-2H-W哚-2-one trifluoroacetic acid Salt set 143924-sp-20091127-2 •362- 201020257 Ηdiphenylmethyl)-3-(2-hydroxy-4-methoxy-5-methylphenyl)-i,3-dihydro-2H- Indole-2-one's 4-methyl-1,-[(2R)-tetrahydrofuran-2-ylmethyl]-3,4-dihydro-2H-spiro[吱,[2,3-g ][l,4]benzoindole-8,3·-吲哚]ΚΓΗ)-one (62%) as a pale yellow solid: mp 138-140 ° C (diethyl ether / hexane); 4 NMR (300 ΜΗζ, CDCI3) (diastereomers) accounted for 7.26 (dd, J = 7.7, 7.7 Ηζ, 1 Η), 7.16-6.99 (m, 3H), 6.29 (s, 1H), 6.122, 6.117 (s, 1H) ), 4.86 (d, J = 8.9 Hz, 1H), 4.61 (d, J = 8.9 Hz, 1H), 4.31-4.21 (m, 1H), 4.13 (dd, J = 4.5, 4.5 Hz, 2H), 3.99 -3.66 (m, 4H), 3.23 (dd, J = 4.5, 4.2 Hz, 2H), 2.87 (s, 3H), 2.07-1.83 (m, 3H), 1.81-1.67 ® (m, 1H); 13C Ruler (75 MHz, CDC13) (diastereomer) &lt;5 17 8.5, 178.3, 156.1, 143.1, 142.9, 139.0, 137.8, 132.7, 132.6, 128.7, 128.6, 123.84, 123.76, 123.2, 116.41, 116, 35, 110.26, 110.22, 109.7, 109.4, 94.4, 80.2, 80.1, 77.3, 76.8, 68.38, 68.35, 64.5, 58.3, 49.2, 44.64, 44.58, 39.0, 29.4, 29.0, 25.9, 25.7 ; MS (ES+) m/z 393.0 (M + 1) 〇 Example 2.31 r-[(2R)-ra Hydroquinone-2-ylindenyl]_纽_螺[吱,[3,2_g][1,3]benzodioxanene-6,3·-吲哚]_2,(1Ή)_ Ketone synthesis

According to the procedure as described in Example 2, and irrelevant changes were made, 3-(7-hydroxy-4Η-1,3·benzodioxanthene-6-yl)-small [(2R)tetrahydrofuran- 2-(2-methyl)-1,3-dihydro-2H-fluorenone replaces p(diphenylmethyl)3 (2hydroxy-4-methoxy-5-mercaptophenyl)_1,3_2 Hydrogen 2H_♦2_2 ketone, obtaining r [(2R) four 143924-sp-20091127-2 -363- 201020257 hydrofuran-2-ylmethyl]-4H-spiro[吱喃[3,2- g][l,3]benzodioxanthene-6,3'-chile]-2'(1Ή)-one (3%) ' is a colorless solid: iH NMR (300 MHz, CDC13) δ 7.38 -6.99 (m, 4H), 6.47 (s, 1H), 6.30 (d, J = 3.6 Hz, 1H), 5.15 (ABq, 2H), 4.89 (d, J = 9.0 Hz, 1H), 4.71-4.61 ( m, 3H), 4.30-4.20 (m, 1H), 3.96-3.64 (m, 4H), 2.10-1.60 (m, 4H); 13C NMR (75 MHz, CDC13) δ 177.8, 177.8, 160.5, 160.5, 153.9 , 142.8, 142.7, 132.3, 132.2, 128.8 (2C), 123.6, 123.3, 122.4, 122.3, 119.6 (2C), 113.9, 109.6, 109.5, 99.2, 91.2, 80.3, 76.9, 68.2, 68.1, 66.2, 57.5 (2C ), 44.7, 44.6, 29.2, 29.0, 25.6, 25.5; MS (ES+) m/z 379.9 (M + l), 401.8 (M +23). Example 2.32

1H Diphenylmethyl)-2,3,6,7-tetrahydrospiro[pyrano[3,2-g]nonene_5,3. Synthesis of bow I 哚]-2'(1Ή)-_

1-(Diphenylfluorenyl)-3-(6-hydroxy-2,3-dihydro-1-benzoindol-5-yl)-1,3-dihydro-2Η-吲哚-2- Suspension of ketone (5.1 g, 11.8 mmol), 1,2-dibromoethane (4.7 g, 25.0 mmol) and carbonic acid (24.4 g, 75.0 mmol) in tetrahydrofuran (200 mL) Stir at argon and ambient temperature for 16 hours and at 50 ° C for 7 hours. The reaction mixture was filtered, and the filtrate was evaporated under reduced pressure. The residue was subjected to column chromatography using dioxane/methanol (100/1_20/1) to give bis-(diphenylmethyl)-2,3,6,7-tetrahydrospiro[ [3,2-g]decene_5,3,_"哚]-2'(1Ή)-net (2.11 g, 39%), colorless solid: MS (ES+) m/z 459.8 (M + l). Example 2.33 143924-SP-20091127-2 •364- 201020257 1'-(Diphenylmethyl)yl 2 3 dihydrospiro[吱3[2 3 g][1,4]benzodioxanthene Synthesis of -8,3,-吲哚]-2,(1Ή)-ketone

I] According to the procedure as described in Example 2, and with irrelevant changes, use 1_(diphenylfluorenyl)-7-fluoro-3-(7-hydroxy-2,3-dihydro-1,4- Benzodioxanthene® Dilute _6_yl Substituted 1-(Diphenylmethyl)-3-(2-hydroxy-4-methoxy-5) from 3-Dihydro-2-indole-2-one ·• mercaptophenyl) 4,3_dihydro 2Η啕哚_2-one, obtained Γ (diphenylmethyl)-7'-carbyl-2'3-dihydrospiro[唉唉[2 3_§][1,4]benzodioxanthene_8,3,_side]-2'(1Ή)-one (55%) ' is a colorless solid: MS (ES+) she 479 9 (M +. Example 2.34 2,2-digas-1'-{[5-(trifluoromethyl)-anthracene-2-yl]methyl} snail [biting and argon [2 3_叩, 3]

Synthesis of stupid and dioxolone-7,3,-吲哚]-2,(1Ή)-ketone

Cf3 according to the procedure as described in Example 2, and with irrelevant changes, using 3-(2,2-difluoro-6-hydroxy-1,3-benzodioxanthene-5-yl) {[5_(Trifluoromethyl)furan-2-yl]fluorenyl}_ι, 3_dihydro 2Η-吲哚 2 ketone to replace diphenyl fluorenyl)-3-(2-hydroxy ice methoxy! Methylphenyl)_u dihydro 2 Η吲哚 2 ketone to obtain 2,2-difluoro-1|-{[5-(trifluoromethyl)pyran-2-yl]methyl} snail [bite喃[2,3々[1,3]benzodioxanthene·7,3'_啕哚]_2ι(1Ή) ketone (55%), grayish white solid

143924-sp-20091127-2 -365- 201020257 体: Melting point 59-60 ° C (recrystallization from the melt); 1H NMR (300 MHz, CDC13) δ 7.37-7.30 (m, 1H), 7.21-7.15 (m , 1H), 7.14-7.07 (m, 1H), 7.02 (d, J = 7.9

Hz, 1H), 6.79-6.74 (m, 1H), 6.72 (s, 1H), 6.44-6.40 (m, 1H), 6.36 (s, 1H), 5.12-4.83 (m, 3H), 4.73 (d, J = 9.1 Hz, 1H) ; 13C NMR (75 MHz, CDC13) δ 176.7, 157.0, 151.8, 144.7, 142.2, 141.7, 141.5, 138.5, 135.4, 132.0, 131.4, 129.6, 128.6, 124.2, 122.4, 120.7, 117.1 , 112.8, 109.6, 109.3, 104.6, 94.4, 80.6, 58.0, 37.1; MS (ES+) m/z 465.7 (M + 1). Example 2.25 2,2-Difluoro-indole-{[5-(trifluoromethyl) olyl-2-yl]methyl} snail [吱,[2,3-fl[l,3] ® benzo Synthesis of dioxolene-7,3'-啕哚]-2\1Ή)-one

3-(2,2-difluoro-6-hydroxy-1,3-benzodioxanthene-5-yl)-1 was used according to the procedure as described in Example 2, and insignificantly changed. -Methyl-1,3-dihydro-2-indole-2-one substituted 1-(diphenylmethyl) each (2-hydroxy-4-methoxy-5-methylphenylindole, 3- Dihydro-2Η-4哚-2-one, 2,2-difluoro-indole-{[5-(trifluoromethyl) fluoran-2-yl]methyl} snail [啥,[2, 3-f][l,3]benzodioxol-7,3'-anthracene-2·(1Ή)-one (10%) as a pale yellow solid: mp 176-178°c (hexane /ethyl acetate); 1H NMR (300 MHz, CDC13) δ 7.39-7.32 (m, 1H), 7.18-7.05 (m, 2H), 6.92 (d, J = 7.8 Hz, 1H), 6.72 (s, 1H) ), 6.40 (s, 1H), 4.96 (d, J = 9.1 Hz, 1H), 4.70 (d, J = 9.1 Hz, 1H), 3.29 (s, 3H) ; 13 C NMR (75 MHz, CDC13) ά 177.0, 157.1, 144.7, 143.1, 138.4, 132.0, 131.7, 129.5, 124.0, 123.8, 122.5, 108.7, 104.8, 94.4, 80.8, 58.2, 26.9; MS (ES+) m/z 331.9 (M + 1) 143924- Sp-20091127-2 -366- (s) 201020257 Example 2.36 2'2-Difluoro-1'-{[3-(Trifluoromethylidene-2-yl)methyl} snail [Cough mer [2 3 _ Cong, 3] benzodioxanthene _7,3, - -one - A groan indol] -2, (1Ή)

According to the procedure as described in Example 2, and with irrelevant changes, φ uses 3_(2,2-difluoro-hydroxy-U-benzodioxanthene-5-yl)-1-{[3 -(Trifluoromethyl acridine-2-yl)indolyl; [,3_dihydro-2-indolyl ketone substituted μ(diphenylfluorenyl)-3-(2-hydroxy-4-methoxy 5--5-methylphenyl)_ι,3-dihydro-2Η-indol-2-one, 2,2-difluoro-1'-{[3-(trifluoromethyl)pyridine 2_基]methyl} snail [wei 卩 卩 卩 [1,3] benzodioxolane _7,3'- qiao 哚]-2, (1 Ή)-ketone (23%), colorless Solid: melting point 200-201 ° C (ether / hexane); 1H NMR (300 ΜΗζ, acetone-d6) ά 8.75 (d, J = 4.1 Hz, 1H), 8.24 (d, J = 7.9 Hz, 1H), 7.62 -7.55 (m, 1H), 7.30-7.22 (m, 2H), 7.10-6.84 (m, 4H), 5.42 (d, J = 17.4 Hz, 1H), 5.22 (d, J = 17.4 Hz, 1H), 5.01 ❹(d, J = 9.2 Hz, 1H), 4.91 (d, J = 9.2 Hz, 1H); 13 C NMR (75 MHz, acetone-de) δ 177.6, 158.1, 153.5, 153.4, 144.9, 144.0, 138.6 , 135.7, 132.8, 129.9, 126.9, 125.3, 124.9, 124.6, 124.0, 123.7, 123.3, 109.9, 106.6, 98Λ 81.3, 58.7, 42.9; MS (ES+) m/z 477.0 (M + 1). Example 2.37 6· - (diphenylfluorenyl)-2·,3',5,6-tetrahydrospiro[benzo[i,2-b:5,4-b]difuran-3,8,-[l,4] Synthesis of oxetene-[2,3-f]吲哚]-7-form Ή)-ketone 143924-sp-20091127-2 -367- 201020257

According to the procedure as described in Example 2, and with irrelevant changes, 6-(diphenylfluorenyl)-8-(6-hydroxy-2,3-dihydro-1-indolofuran-5-yl was used. )_2,3,6 8_ Tetrakis-7H-[1,4]-oxodecene-[2,3-f]p?丨嗓-7-one-substituted ι_(diphenylfluorenyl)_ 3-( 2-hydroxy-4-decyloxy-5-methylphenyl)_u_dihydro-2H_吲哚_2•one, which gives 6'-(diphenylmethyl)-2|, 3', 5, 6-tetrahydrospiro [stupid [U_b: 5,4,7]]difuran_3,841,4] sulphate and sulphate [2,3-f]吲嗓]-7'(6Ή)-net ( 67%) as a colorless solid: MS (ES+) m/z 504.0 ( Μ + 1). Example 2.38 3|-(4-decyloxyindenyl)-5,6-dihydrospiro[benzo[[7:5,4,7]]difuran-31,pyrrolo[3,2-f]quina Synthesis of porphyrin]_2,(3Ή)-_

According to the procedure as described in Example 2, and irrelevant changes were made, 1-(6-hydroxy-2,3-dihydro-indole-benzofuran-5-yl)_3_(4-methoxybenzyl) was used. Substrate _13_ diar-argon-2 Η-pyrrolo[3,2-f]quinolin-2-one to replace μ(diphenylmethyl)·3 (2 hydroxy_4_methoxy-5-methylphenyl)_ι , 3_Dihydro 2η_ρ5丨哚_2-ketone, to obtain 3,_(4-methoxy lower)-5,6-monohydrospiro[benzo[12_b:5,4_b,]difuran_3 Γ Pyrrolo[3 2 quinquinine]-2(3Η)-one (9%) 'Yellow solid: mp 169_17〇〇c; 1H NMR (300 MHz, CDC13) δ 8.75 (s, 1H), 8.10 (m , 1H), 7.92 (m, 1H), 7.43-7.28 (m, 4H), 143924-sp-20091127-2 (S) -368· 201020257 6.92-6.86 (m, 2H), 6.51 (s, 1H), 6.44 (s, 1H), 5.17-5.06 (m, 2H), 4.97-4.88 (m, 2H), 4.58-4.49 (m, 2H), 3.79 (s, 3H), 3.09-2.82 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 179.1, 162.2, 161.0, 159.3, 148.0, 144.6, 140.2, 130.9, 128.8, 127.8, 127.6, 124.8, 122.4, 120.4, 119.8, 118.9, 114.4, 113.9, 93.4, 79.6, 72.4, 58.5, 55.3, 43.9, 29.0; MS (ES+) m/z 451.0 (M + 1). Example 2.39 6-Hydroxy-indole-(4-methoxybenzyl)-2'-keto-oxime, 2,-dihydrospiro[1-benzofuran-3,3,- 丨嗓]-5 - synthesis of carbonitrile

'2,4-Dihydroxy-5-[l-(4-methoxyindolyl)-2-keto-2,3-dihydro-1Η-indol-3-yl]benzene under nitrogen Add carbonitrile (23.8 g, 73.0 mmol) to a stirred solution of carbonitrile (9.40 g, 24.3 mmol) and gas-based Ethylene (4.40 mL '60.4 mmol) in tetrahydrofuran (250 mL). ). The reaction mixture is

X 200 ml) extraction mixture. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue is subjected to column chromatography and eluted with ethyl acetate to give 6-hydroxy-indole-(4-decyloxybenzyl)-2'-ketodihydrospiro[μbenzofuran_3, 3, _ 4 哚]-5-carbonitrile (2.57 g, 26%): melting point 112-114 ° C (ethyl acetate / hexanes); !H NMR (300 MHz, DMSO-d6) δ 11.32 (s, 1H), 7.29-7.16 (m, 4H), 7.02-6.97 (m, 2H), 6.89-6.85 (m, 3H), 6.54 (s, 1H), 4.93-4.77 (m, 4H), 3.68 143924-sp -20091127-2 -369- 201020257 (s, 3H) ; MS (ES+) m/z 398.8 (Μ + 1). Example 2.40 6-Gasyl-indole-(4-methoxyoxy)-2'-keto-oxime, 2'-dihydrospiro[1-benzo-chewing_3,3,_峋哚]- Synthesis of 5-carbonitrile

Under nitrogen, 2-fluoro-4-hydroxy-5-[l-(4-decyloxyindolyl)-2-keto-2,3-dihydro-1H-indol-3-yl] Clandile nitrile (10.50 g, 27.03 mmol) with gas-based iodine (5.00 ml '68.7 mmol) in tetrahydrofuran (2 mL) with n,N-dimethylformamide ( In a stirred solution of 50 ml), a carbonic acid planer (26 4 g, 81.02 mmol) was added. The reaction mixture was stirred at ambient temperature for 2 hrs and filtered through a pad. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate/hexane (1/3) to give 6-fluoro-l-lL (4-methoxybenzyl)-2'-keto-oxime, 2 '-Dihydrospiro[1-benzopyrene]-5-carbonitrile (5.27 g '48%): mp 142-143. (: ; 4 NMR (300 MHz, CDC13) 5 7.29-7.23 (m, 3H), 7.11-7.02 (m, 2H), 6.89-6.85 (m, 4H), 6.77 (d, J = 9.0 Hz, 1H) , 5.12-4.75 (m, 4H), 3.78 (s, 3H); MS (ES+) m/z 400.7 (M + 1). Example 2.41 Γ-(4-methoxybenzyl)-3_indenyl snail Synthesis of [p-antho-benzo-isoxazole_7,3,_β丨哚]-2·(1Ή)-ketone 143924-sp-20091127-2 -370- 201020257

Following the procedure as described in Example 2, and performing an insignificant change' using 3-(5-carbyl-3-methyl-iso-p-iso- 0--6-yl)-1-(4-methoxy爷 1,3-dihydro-2H-indol-2-one substituted 1_(diphenylmethyl)-3-(2-hydroxy-4-oximeoxy-5-methylphenyl)-13 -Dihydro-2H-W哚-2-one, obtaining l'-(4-methoxybenzyl)-3-indole

Point 183-184 ° C (ethyl acetate / hexane); NMR (300 MHz, CDC 13) &lt;5 7.29-7.21 (m, 3H), 7.13-7.10 (m, 1H), 7.05 (s, 1H), 7.03-6.98 (m, 1H), 6.89-6.86 (m, 3H), 6.82 (s, 1H), 5.07-5.00 (m, 2H), 4.79-4.74 (m, 2H), 3.78 (s, 3H), 2.51 (s, 3H) ; MS (ES+) m/z 412.8 (M + 1). Example 2.42 4·-Bromo-1'-(diphenylindenyl)-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene-8 ,3·-吲哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 2, and irrelevant changes were made, 4-bromo-1-(diphenylmethyl) each (7-hydroxy-2,3-dihydro- 14 benzodioxan) was used. Rare-6-yl)-1,3-dihydro-2Η-吲哚_2-one substituted 1-(diphenylmethyl)_3_(2-hydroxyindoleoxy-5-fluorenyl) Hydrogen 2 Η吲哚 2 ketone, obtained bucket, bromo (di-m-methyl) 2,3-hydrogen snail [pf sulphur [^ phantom (4) benzodioxanthene _8, 3, · Qiao丨143924^sp-20091127-2 •371- 201020257 哚]-2'(1Ή)-ketone (66%) ' is a colorless solid: 1H NMR (3〇〇MHz, DMS〇_d6) δ 7.47-7.16 (m , 12H), 6.85 (s, 1H), 6.82-6.76 (m, 1H), 6.57 (s, 1H), 5.92 (s, 1H), 5.66 (ABq, 2H), 4.22-4.14 (m, 4H). Example 2.43 4'-Bromo-1'-mercapto-2,3-dihydrospiro[吱,[2,3_g][1,4;^and dioxanedecene_8,3'_吲哚]-2,(1Ή)-ketone synthesis

4-Bromo-3-(7-hydroxy-2,3-dihydrobenzodioxanthene thiol-1 was used according to the procedure as described in Example 2.40, and irrelevant changes were applied. , 3-dihydro-2-indole-2-one substituted 2_fluoro-4-4-hydroxy-5-1(4-methoxybenzyl)-2-keto-2'3-dihydro-1Η -吲哚_3_yl;|benzonitrile, 4,-bromo-indenyl, fluorenyl-2,3-dihydrospiro[[---KM]-benzodioxanthene_8 ,3,_吲哚]_ 2(lH)-ig (95%) . lH NMR 〇〇〇MHz&gt; CDC13) &lt;5 7.23-7.14 (m, 2H), 6.87-6.79 (m, 1H), 6.43 (s, 1H), 6.16 (s, 1H), 4.93 (ABq, 2H), 4.22-4.07 (m, 4H), 3.24 (s, 3H) ; MS (ES+) m/z 387 9 (M + 1χ 389 9 (M + ^. Example 2.44 1'-(Diphenylmethyl)-t-fluoro- 2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene- Synthesis of 8,3'-吲哚],2,(1Ή)-ketone

143924-sp-20091127-2 -372- 201020257 ene-6-yl)-l,3-dihydro-2H-indol-2-one replacing 1-(diphenylmethyl)-3-(2-hydroxy- 4-methoxy-5-methylphenyl)-1,3-dihydro-2H-indol-2-one, obtaining 1·-(diphenylmethyl)benfluoro-2,3-dihydro Snail [Ethyl[2,3-g][l,4]benzodioxanthene-8,3'-&lt; 哚]-2'(1Ή)-one (83%) as a colorless solid : melting point 196-198 ° C; 1H NMR (300 MHz, DMSO-d6) δ 7.46-7.26 (m, 10 Η), 7.19 (ddd, J = 8.2, 8.2, 6.1 Hz, 1H), 6.89 (s, 1H), 6.83 (dd, J = 8.9, 8.9 Hz, 1H), 6.50 (s, 1H), 6.46 (d, J = 8.0 Hz, 1H), 6.09 (s, 1H), 4.83 (q, J = 9.6 Hz, 2H ), 4.14 (dd, J = 5.3, 3.2 Hz, 4H); 13 C NMR (75 MHz, DMSO-d6) δ 176.3, 157.9 (d, 1 Jc. F = 247 Hz), 144.3, 143.8 (d, 3) Jc-F= 8.4 Hz), 137.2 (d, 3 JC-F= 13.6 Hz), 130.5 (d, 3 JC-F= 8.6 Hz), 128.1, 127.8 (d, 3JC.F= 9.0 Hz), 119.2, 117.3 (d, 2JC.F = 19.0 Hz), 110.4, 110.0 (d, 2Jc.p = 19.7 Hz), 107.8 (d, 4Jc.F = 2.8 Hz), 98.7, 77.5, 64.1, 63.5, 58.6, 55.8 ( d,4 JC.F= 2.8 Hz) » MS (ES+) m/z480.0 (M + 1), Example 2.45 Γ-(4-Fluorophenyl)-2,3-dihydrospiro And [2,3-g] [l, 4] benzo-dioxan-5-ene -8,3% Shu indol] -2 '(1Ή) - Synthesis of Gang

Using 1-(4-fluorophenyl)-3-(7-hydroxy-2,3-dihydro-indole, 4-benzodioxane according to the procedure described in Example 2, and carrying out irrelevant changes Terpene _6_yl)-1,3-dihydro-2Η-indol-2-one replacement μ(diphenylmethyl)_3_(2-hydroxy-4-indolyl-5-methylphenyl) -1,3-Dihydro-2Η-吲哚_2-one, obtaining ι,·(4-fluorophenyl)-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene _8,3,_吲哚]_2Ι(1Ή), 143924-sp-20091127-2 -373- 201020257 (71%), as a colorless solid: melting point 210-212 ° C; 1HNMR (300MHz, DMSO-dg) δ 7.63-7.59 (m, 2H), 7.45-7.39 (m, 2H), 7.31-7.23 (m, 2H), 7.10 (dd, J = 7.3, 7.3 Hz, 1H), 6.75 (d, J = 7.8 Hz, 1H), 6.52 (s, 1H), 6.46 (s, 1H), 4.80 (q, J = 9.4 Hz, 2H), 4.21-4.09 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) (5 176.1, 161.2 (d, 1JC-F= 245 Hz), 154.6, 144.1, 143.0, 137.7, 131.6, 130.4 (d, 4 JC.F = 2.9 Hz), 129.4 (d , 3 JC.F= 8.9 Hz), 128.6, 123.7, 123.3, 121.1, 116.4 (d, 2 Jc-F= 22.8 Hz), 111.5, 109.0, 98.6, 79.6, 64.1, 63.5, 57.2; MS (ES+) m /z 390.0 (M + 1). Example 2.46 Γ-(diphenylmethyl) -4'-trolin-3-yl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚] -2'(1 ugly)-ketone synthesis

Packed in a 10 ml microwave reaction vessel with 4,-bromo-indenyl-(diphenylfluorenyl) 2,3-dihydrospiro[pf-pyrano[2,3-g][l,4]benzoic acid Oxygen olefin oxime]-2, (1 Ή)-ketone (0.38 g ' 1.40 mM), bismuth (triphenylphosphine) (〇.08 gram, 〇 14 mmol), quinol-3 --Dihydroxyborane (0.20 g '2.3 mmol), 2 Μ aqueous sodium carbonate solution (1.8 liter) and hydrazine, hydrazine-methyl methacetamide (3 ml). The reaction mixture was irradiated in a microwave reactor at 150 ° C for 15 minutes. The reaction was repeated, and the two reaction mixtures were combined, poured into distilled water (75 ml), and extracted with ethyl acetate (150 ml). The combined organic extracts were washed with water (3×·································· The residue was purified by column chromatography and eluted with a gradient of 20% to 50% of ethyl acetate in hexane to give bis(diphenylmethyl)_4, _ _ _ _ _ _ _ _2 ,3_Dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3|_啕哚]-2,(1Ή)-ketone (0,29 Gram '35%) as a pale yellow solid: MS (ES+) _ 589 〇 (Μ + 丄). Example 2.47 Γ-(Diphenylmethyl)-4'-(4-phenoxyphenyl)_2,3_dihydrospiro[吱,[2,3_g][1,4]

According to the procedure as described in Example 2.46, and irrelevant changes were made, 4-phenoxyphenyl dipyridyl (4) was substituted with a perylene group to give a ruthenium-(diphenylmethyl)- 4·-(4-phenoxy Am ^ ^ _ milk base)-2,3-ditopyrro[吱,[2,3_g]

[1,4]benzodioxanthene-8,3·-吲唼]0,n,u,/nnrw, 5 eucalyptus]-2 (1Ή)-ketone (99%), as a colorless solid: MS (ES+) m/z 630.0 (M + 1). Example 2.48 Synthesis of fluorene-(diphenylfluorenyl)-2'--yl-1 2'-dihydrospiro[1-benzofuran_3,3,_吲哚]carbonitrile

Packing 6-Molyl-1'-(diphenylmethyl) spiro[μ 143924-SP-20091127-2, 375- 201020257 benzofuran-3'3'-(9)哚]-2 in a 10 ml microwave reaction vessel '(1Ή)-ketone (0.51 g, u mmol), nickel dihydrated nickel hexahydrate (0.25 g, 1.1 mmol), sodium cyanide (〇.1 g, 21 mmol) and 1 -Methyl-2-tetrahydropyrrolidone (1 ml). The solution was irradiated in a microwave reactor at 200 ° C for 20 minutes. The solution was allowed to cool to ambient temperature, diluted with ethyl acetate (25 mL) and filtered. The filtrate was washed with brine (3 mL 15 mL), dried over magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography and eluted with ethyl acetate in a 15% to 5% gradient in hexane to give bis-(diphenylmethyl)-2'-keto oxime, dihydrol Snail []L_benzofuran_3,3,_B 丨哚]-6-carbonitrile (0.50 g, 100%) as a colorless solid: 1H NMR (3 〇〇MHz, _ CDC13) δ 7.44- 7.22 (m, 10H), 7.21-7.18 (m, 1H), 7.14-6.93 (m, 5H), 6.72 (d, J = 7.8 Hz, 1H), 6.55 (d, J = 7.5 Hz, 1H), 5.07 (d, J = 9.2 Hz, 1H), 4.80 (d, J = 9.2 Hz, 1H). Example 2.49 5 -Bromo-indenyl-(ρ-pyridin-2-ylindenyl)_2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Synthesis of -8,3'-θ丨嗓]-2'(1Ή)-ketone

Small 5-(bromo-2-yl-2-ylmethyl) 4,3_2 Hydrogen 2 Η, 丨哚 2 ketone (2 gram, 4 4 〇 millimolar) in a solution of anhydrous hydrazine, hydrazine dimethyl dimethyl carbamide (25 ml), adding carbonic acid planing (4.30 g' 13·2 mmol) with chloroiododecane (0.85 g, 4.9 mmol). The solution was stirred at ambient temperature for 16 hours and poured into water (100 mL). The mixture was extracted with ethyl acetate (3×50 ml), and the combined ethyl acetate extracts were washed with 143924-sp*20091127-2 -376-201020257 brine (2×35 ml), dried over magnesium sulfate, filtered, and Concentrate in vacuo. The residue was triturated in dioxane/diethyl ether (2/5, 14 mL), and then 5-&gt; odor- Γ-(ρ ratio β _2 曱 曱 ))-2, 3- Hydrogen snail [[,,,,,,,,,,,,, It is a beige solid. Melting point &gt; 250 ° C (dichlorohydrazine / acetonitrile); ^ NMR (300 MHz, CDC13) δ 8.57-8.52 (m, 1H), 7.69-7.61 (m, 1H), 733 -7.27 (m, 3H), 7.26-7.16 (m, 1H), 6.77 (d, J = 8.3 Hz, 1H), 6.49 (s, 1H), 6.30 (s, 1H), 5.16 (d, J = 15.8 Hz, 1H), 4.97-4.87 (m, 2H), 4.64 (d, J = 9.0 Hz, 1H), 4.22-4.08 (m, 4H) ; 13 C Θ NMR (75 MHz, CDC13) (5 176.9, 155.2 , 155.1, 149.6, 144.9, 141.1, 138.4, 137.2, 134.2, 131.7, 127.0, 122.9, 121.7, 120.4, 116.1, 111.7, 111, 1, 99.5 80.0, 64.5, 63·9, 58·2, 46.1; MS ( ES+) m/z 465.0 (M+ l), 467. 〇 (M+l). Example 2.50 2-keto-indole-indolepyridin-2-ylmethyl)-1',2,2',3- Synthesis of tetrahydrospiro[吱,[2,3_g][i,4]benzodioxanthene-8,3'-吲嗓]-5'-carbonitrile

According to the procedure as described in Example 2.48, and with irrelevant changes, use 5-'s shoulder-Γ-〇-bipyridin-2-ylindenyl)_2,3_dihydrospiro[biting and [2 3_g ] [14] benzodioxanthene-8,3·-吲哚]_2, (1,Η)-_substituted 6-bromo-(diphenylmethyl) snail [1- benzofuran-3 , 3 -啕哚]-2'(1Ή)-ketone, 2,-keto-1,-(pyridine-2-ylmethyl)-indole, 2,2',3-tetrahydrospiro[furan [2,3-g][l,4]benzodioxanthene _8,3,_ sapwood]-5-carbonitrile (83%) as a colorless solid: m.p. 198. 〇 (ethyl acetate / hexane), 1H NMR (300 MHz, CDCI3) 6 8.56-8.52 (m, 1H), 7.65-7.68 (m, 1H), 143924-sp-20091127-2 -377· 201020257 7.51 ( Dd, J = 8.2, 1.4 Hz, 1H), 7.40-7.38 (m, 1H), 7.30-7.18 (m, 2H), 7.01 (d, J = 8.2 Hz, 1H), 6.51 (s, 1H), 6.29 (s, 1H), 5.20 (d, J = 15.8 Hz, 1H), 4.96 (d, J = 15.5 Hz, 1H), 4.92 (d, J = 8.9 Hz, 1H), 4.64 (d, J = 9.1 Hz , 1H), 4.23-4.09 (m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 177.1, 155.2, 154.4, 149.7, 146.0, 145.1, 138.6, 137.2, 133.9, 133.4, 127.2, 123.1, 122.0, 119.8 , 118.7, 111.6, 110.2, 106.7, 99.7, 79.8, 64.5, 63.9, 57.8, 46.1; MS (ES+) m/z 412.0 (M + 1). Example 2.51 5|-Momot-1'-(diphenylmethyl)-2,3-dihydrospiro[N,3-phantom [1,4]benzodioxanthene-8, Synthesis of 3'-吲哚]-2,(1Ή)-ketone

According to the procedure as described in Example 2, and irrelevant changes were made, 5-&gt; odor-1-(diphenylmethyl) each (7 lightly -6-yl)-1'3-dihydro was used. -2Η,哚-2-ketomethoxy-5-methylphenyl w'3 dihydrobenzyl)-2,3-dihydrospiro[唉,[2,3 哚]-2, (1 ,H)-ketone (76%), colorless solid diphenylmethyl)-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene gas ·2Η1哚-2- Ketone replacement of 1-(diphenylhydrazinyl)-3-(2-hydroxy-4-hydro-2-indole-2-indole-2-one to give 5,-bromo-indenyl-(dioxaspiro-bromo[2] , 3-g][l,4]benzodioxanthene _8,3'4丨(Μ+1). Colorless solid: MS (ES+) m/z 539.9 (Μ + 1), 541.1 Example 2.52 Γ-(diphenylmethyl)-5'-methyl_2 3_di-methyl-2,3-dihydrospiro[吱3[g]g[1,4]benzodioxan Synthesis of ~8,3'·吲哚]-2,(1Ή)-ketone 143924-sp-20091127-2 - 378 · 201020257

In a 10 ml reaction vessel, tri-o-tolylphosphine (0.022 g, 0.075 mmol), diacid (〇013 g, 0.020 mmol), triethylamine (〇13 g 1.30) were added. Millol), hydrazine, hydrazine-dimethyl decylamine (j 5 ml), tetradecyltin (〇2 gram, 1.1 millimolar) and broad (diphenyl fluorenyl) 5, base _2 , 3_ dihydrospiro [eats and [2,3 g][l,4] stupid and monooxodecene_8 3,吲哚]_2, (1Ή) ketone (〇5〇g, ο.% Million φ Moel). The reaction vessel was sealed, heated at u〇〇c for 16 hours, allowed to cool to ambient temperature, and poured into water (5 mL). The mixture was extracted with ethyl acetate (2 mL) and the combined organic extracts were washed with brine (2 ml), dried with sulphuric acid, filtered, and concentrated in vacuo. The residue was purified by e-column chromatography and eluted with 15% ethyl acetate in hexane, and then recrystallized from the mystery, and the heart was methyl)5, methyl-2,3 dioxo喃[2,3-g][l,4]benzo-oxoindole _8,3,4嗓]-2, (ΐΉ)-class (1)% gram, φ 86%) is a colorless solid · MS (Es+) m/z 476.0 (Μ + 1). Example 2.53 ^Methyl-2, every -1',2,2,,3·4 snail [cough and [2,3_g][1,4] benzodioxan olefinic acid benzene vinegar synthesis

Adding 4,-Molyl-r-methylspiro[吱然(10) 143924-sp-20091127-2 -379. 201020257 [1,3] benzodioxolan-7, in a high pressure steel reaction vessel, 3'-Linghuao]_2, (i,h)-ketone (10 g, 26 mmol), palladium acetate (0.35 g '1.55 mmol), 1,3_bis(dicyclohexylfluorene)propane double (tetrafluoroborate) (0.64 g, 1. 〇 millimol), phenol (2 92 g, 31 〇 mmol), potassium carbonate (5.34 g '39.8 mmol), activated 4 A molecular sieve ( 4.00 g) and N,N-didecylguanamine (3 〇.〇 ml). The reaction vessel was purged with nitrogen for 1 Torr, sealed to a pressure of 15 psi with carbon monoxide, and stirred at 12 ° C for 82 hours. The mixture was poured into water (1 mL) and extracted with ethyl acetate (3 EtOAc). The combined organic extracts were washed with brine (2×50 mL). % to 75% of the gradient solution is dissolved 'subsequently recrystallized from the dichlorocarbyl / diethyl ether to give 1,1 -mercapto-2,-keto-1',2,2',3-tetrahydrospiro [2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-4·-carboxylic acid phenyl ester (3.30 g '30%) 'as colorless solid: melting point 184 -186 ° C (diethyl ether); 1H NMR (300 MHz, CDC13) δ 7.85 (d, J = 8.0 Hz, 1H), 7.49 (dd, J = 7.9, 7.9 Hz, 1H), 7.35-7.11 (m, 4H ), 6.84-6.78 (m, 2H), 6.24 (s, 1H), 6.12 (s, 1H), 5.11 (d, J = 8.5 Hz, 1H), 4.87 (d, J = 8.5 Hz, 1H), 4.18 -4.05 (m, 4H), 3.29 (s, 3H); MS (ES+) m/z 451.92 (M + 23). ® Example 2.54 1'-{[3-(Trifluoromethyl)P-pyridin-2-yl]methyl b 7,8-dihydrospiro[1,4-dioxopinene [2,3- g][l,3]benzodioxanthene-4,3'-吲哚]-2·(1Ή)-synthesis of brewing 1

143924,sp-20091127-2 -380- 201020257 Under a argon atmosphere, in a 100 ml flask, 3-hydroxy_3_(7-hydroxy_23_-argon-1,4-pentandoxydioxene-6 was charged. -yl)-1-{[3-(trifluoromethyl)p than bite_2_yl]methyl}-1,3-dihydro-2HM丨哚-2-one (0.46 g, 1.0 mmol) ), gas-based iodonane (0.36 g, 2.0 mmol), hydrazine hydride (1.3 g, 4.0 mmol) and anhydrous tetrahydrofuran (50 mL). The reaction mixture was heated under reflux for 3 hours, allowed to cool to ambient temperature and filtered. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography and eluted with ethyl acetate in 二 至 至 至 至 至 至 至 , , , , , , , , [ [ [ 三氟 三氟Methyl)pyridine_2_yl]methyl}·7,8_ ® dihydrospiro[1,4-dioxolynene[2,3-g][l,3]benzodioxanthene _4,3,_ρ?丨嗓]-2'(1Ή)-one (0.16 g, 34%), as an off-white solid: melting point &gt; 〇 (methanol); 1H NMR (300 MHz, CDC13) 5 8.65 (d, J = 4.5 Ηζ, 1 Η), 7.96 (d, J = 7.8 Hz, 1H), 7.35-7.14 (m, 3H), 6.95-7.03 (m, 1H), 6.68 (s, 1H), 6.57 (d, J = 7.8 Hz, 1H), 6.52 (s, 1H), 5.70 (ABq, 2H), 5.21 (ABq, 2H), 4.25-4.01 ( m, 4H) ; 13C NMR (75 MHz, CDC13) 5 176.3, 152.3, 152.2, 147.8, 144.1, 143.3, 138.9, 134.3, 134.2, 134.2, 134.1, 130.7, 130.2, 129.2, 125.6, 125.2, 124.8, 124.4, 124.0, 123.5, 122.2, 122.0, 114.9, 114.2, 108.7, 105.3, 88.3, 77.2, 64.5, 64.0, 41.8, 41.7. Example 2.55 1'-(Diphenylmethyl)-9-1yl-2,3-dihydro-spiro[N-[2,3-g][l,4]benzodioxanthene-8 , 3'-啕哚]-2Χ1Ή)-keto synthesis

143924-sp.20091127-2 -381- 201020257

Using 1-(diphenylmethyl)_3_(5-fluoroyl-7-hydroxyl) and performing irrelevant changes,

-/ ^ - Rolling - ZH-吲哚_2_ ketone) Benzyl-2,3-dihydro _ sulphide and yang gamma] benzo ♦ flower] -2, _, pottery, as an off-white solid: -7-Phosyl-2,3-dihydro-i,4-benzodioxanthracene substituted Ηdiphenylmethyl)-3-(2-hydroxy-4-hydro-:2H-啕哚-2 -ketone, obtaining ι·_(diphenylcarbamate[2,3-g][l,4]benzodioxolene-8,3,_· hexane white solid: MS (ES+) m/z 479.8 (M + example 2.56 Η-benzyl)-7,8-dihydrogen, 6Η-4 tired [biting and [2,3_g] octagonal _3,3,_+)]-φ 2'(1H) -ketone synthesis

According to the procedure as described in Example 2, and irrelevant changes were made, 1-(diphenylmethyl)_3_(6-hydroxy-3,4-dihydro-2-indole-1-decene-7-dihydro-2H was used. -V?丨嗓-2- Brewing I Replacement 1_(Diphenylmethyl)_3_(2_Hydroxy-bromomethoxy-5-methyl adenyl)-1,3-Dihydro-2Η-吲哚-2 -_, obtain 1_(diphenylmethyl)_7 8 · dihydro _ _ snail [biting mers [2,3-g] octagonal _3,3,-吲哚]-2, (1 Η)-ketone (93%), as an off-white solid: MS (ES+) m/z 460.0 ( Μ + 1). Example 2.57 Η 苯 苯 ) Η丨哚 Η丨哚 , , , , , , , 2 2 2 2 2 Synthesis of [l]benzofuran]-2(m)-one 143924-sp-20091127-2 -382- 201020257

Following the procedure as described in Example 2, and performing irrelevant changes,

〇[2'3-f][l] benzofuran 2 (1H&gt; ketone (54%), as an off-white solid: MS (Es+) heart 460.2 (M + 1) 〇 Example 2.58 1-(Diphenylmethyl) Synthesis of Η丨嗓3,3% dextran [2,3&lt;1(1)benzofuran]_2(10)-ketone 5,5-monooxide

In the case of 1-(diphenylmethyl)spiro 5丨哚-3,3'-sulfeno[2,3-f][l]benzofuran]_2(1H)-one (1.12 g ' 2.44 mmol) In a solution of dichlorocarbyl (50 ml), 3-gas perbenzoic acid (77% w/w, 0.65 g, 2.9 mmol) was added at ambient temperature' and the mixture was stirred 16 hour. The reaction mixture was diluted with EtOAc (EtOAc m.) The residue is purified by column chromatography and eluted with ethyl acetate in a 0% to 20% gradient of dioxane to give 1-(diphenylmethyl)spirobium 5丨哚-3,3· -thieno[2,3-f][l]benzofuran 143924-SD-20091127-2 -383- 201020257 ]]-2(1H)-one 5,5'-dioxide (0.98 g, 82% ), as an off-white solid: MS (ES+) m/z 492.0 (Μ + 1). Example 2.59 Synthesis of l'-(- fluorenyl) snail [吱,[3,2-e][2,l,3]benzoxadiazole_8 3Lp5丨 哚]-2'(1Ή)-ketone

According to the procedure as described in Example 2, and performing irrelevant changes, the instrument | using 1-(diphenylmethyl)_3_(5-hydroxy-2, ι,3-benzoxadiazole_4_yl) 4,3-Dihydro-2Η-throin-2-one substitution 1_(diphenylmethyl) each (2-hydroxylmethoxy-5-methylphenyl)-1,3-dihydro-2Η- Indole-2-one, obtaining r_(diphenylfluorenyl) snail [biting and arranging [3,2_e] [2,1,3] and the number of a saliva ·8,3-4丨嗓]-2' (1Ή)-ketone (50%) 'is a colorless solid: 1 η NMR (300 MHz, CDC13) δ 7.82 (d, J = 9.6 Hz, 1H), 7.58-6.92 (m, 15H), 6.55 (d, J - 7.8 Hz, 1H), 5.25 (d, J = 9.3 Hz, 1H), 4.99 (d, J = 9.3 Hz, 1H); MS (ES+) m/z 446 (M + 1). Example 2.60

6-Chloro-r_G methyl)-2,3-dihydrospiro[吱,[3,2_η to ,4]benzodioxanthene-9,3'-吲哚]-2, (1Ή )-ketone synthesis

CI

Follow the procedure as described in Example 2.40 and perform an insignificant change 143924-sp-20091127-2 •384- 201020257 using 3-(7-chloro-6-hydroxy-2,3·dihydro-M_benzene And dioxanthene _5_yl)+(diphenylmethyl)-1,3-dihydro-2H-indole-2-one substituted 2-fluoro-4-hydroxy-5-[l-( 4-decyloxybenzyl)-2-keto-2,3-dihydro-1H-indol-3-yl]benzonitrile to give 6-chloro-indole-(diphenylfluorenyl)-2 ,3-dihydrospiro[furo[3,2-benzodioxanthene-9,3Wh]-2'(1Ή)-one (65%) ' is a colorless solid: ιΗ (3〇 〇·ζ, CDC13) δ 7.42-7.26 (m, 10H), 7.20-7.15 (m, 1H), 7.11 (s, 1H), 7.03-6.95 (m, 2H), 6.78 (s, 1H), 6.50- 6.45 (m, 1H), 5.02 (d, J = 8.7 Hz, 1H), 4.76 (d, J = 8.7 Hz, 1H), 4.12-3.84 (m, 4H) ; MS (ES+) m/z 496,2 (M + 1). Example 2.61 Synthesis of 1'-(diphenylmethyl)-5,6-difluorospiro[1-benzopyrano_3,3'-by-side]_2ι(1Ή) ketone

3-(4,5-Difluoro-2-hydroxyphenyl)-1-(diphenylmethyl)_ι,3_dihydro _ was used according to the procedure as described in Example 2, and irrelevant changes were applied. 2Η-ν 丨嗓 丨嗓-2-one replacement of 1-(diphenylfluorenyl)-3-(2-hydroxy-4-decyloxy-5-methylphenyl)-1,3-dihydro-2H- W哚-2-ketone, Γ-(diphenylmethyl)_5,6-difluorospiro[1-benzofuran_3,3'_吲哚]-2'(1Ή)-one (70%) ' is a colorless solid: melting point 213-216. (: ; 1H NMR (300 MHz, CDCI3) δ 7.41-7.26 (m, 10H), 7.15-7.12 (m, 1H), 7.08-6.97 (m, 3H), 6.78 (dd, J = 10.5, 6.3 Hz, 1H), 6.54 (d, J = 8.4 Hz, 1H), 6.44 (dd, J = 9.0, 7.8 Hz, 1H), 5.03 (d, J = 9.0 Hz, 1H), 4.77 (d, J = 9.3 Hz, 1H) ; 13 C NMR (75 MHz, CDCI3) δ 176.8, 156.6 (d, J = 11.0 Hz), 151.2 (dd, JC.F = 248.2, 14.5 Hz), 145.6 (dd, JC.F= 241.5, 13.9 Hz), 141.7, 137.4, 137.1, 131.5, 128.8, 128.8, 128.7, 128.3, 128.3, 128.1, 128.0, 124.2 (dd, J = 6.4, 3.3 Hz), 123.8, 143924-sp-20091127-2 •385 - 201020257

57.5 ; MS (ES+) m/z 440.2 (Μ + 1) 〇 Example 2.62 1-(Diphenylmethyl)-5',6',7',8'-tetrahydrospiro(tetra)anthracene _3,3,_ Examining the synthesis of [2,3-7]furan]_2(10)_ ketone

According to the procedure as described in Example 2, and irrelevant changes were made, 1-(diphenylfluorenyl)-3-(3-hydroxy-5,6,7,8-tetrahydroindol-2-yl) was used. -1,3-Dihydro-2H-indole-2-indole substituted 1-(diphenylmethyl)-3-(2-hydroxy-4-methoxy-5-mercaptophenyl)-1,3 -Dihydro-2H-chatty-2-one, 1-(diphenylhydrazinyl)-5,6,7,8,4-tetrahydrospirobium-3,3'-indole[ 2,3-b]biting]-2(1H)-嗣(81%) as a colorless solid: iHNMRQOO MHz, CDC13) δ 7.37-7.32 (m, 10H), 7.17-7.14 (m, 1H), 7.07 (s, 1H), 7.05-6.94 (m, 2H), 6.67 (s, 1H), 6.52 (d, J = 7.6 Hz, 1H), 6.33 (s, 1H), 4.96 (d, J = 8.9 Hz, (H, 4H) + 1). Example 2.63 4',5--Didecyloxy-1·-{[5-(trifluoromethyl)furan-2-yl]indolyl}-2,3-dihydrospiro[furo[2,3 -g] Synthesis of [l,4]benzodioxanthene 哚]-Τ(1Ή)-one

143924-sp-20091127-2 -386- 201020257 Following the procedure as described in Example 2, and carrying out irrelevant changes, 3-(7-hydroxy-2,3-dihydro-1,4-benzoic acid was used. Oxadecene _6-yl)-4,5-dimethoxy-1-{[5-(trifluoromethyl)p-pentan-2-yl]methyl}-l,3-dihydro- 2H-W哚-2-one replacement of 1-(diphenylindenyl)-3-(2-hydroxypipemethoxy-5-methylphenyl)-1,3-dihydro-2H-choline-2 -ketone' obtains 4',5'-dimethoxy-i,_{[5-(trifluoromethyl) succinyl-2-yl]methyl}-2,3-dihydrospiro[啥[2,3-g][l,4]benzodioxanthene p-]-2'(1Ή)-one (77%): m.p. 62-65°C; 1H NMR (300 MHz, CDC13) 5 6.80 (d, J = 8.4 Hz, 1H), 6.74-6.69 (m, 1H), 6.62 (d, J = 8.4 Hz, 1H), 6.45 (s, 1H), ® 6.38-6.32 (m, 1H) , 6.20 (s, 1H), 4.90 (ABq, 2H), 4.85-4.81 (m, 2H), 4.18-4.05 (m, 4H), 3.78 (s, 3H), 3.40 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.0, 155.6, 152.3, 152.2, 149.9, 146.6, 144.6, 137.9, 135.1, 125.0, 120.3, 112.7, 111.1, 109.2, 103.7, 99.1, 78.2, 64.5, 63.9, 60.4, 57.7, 56.3 , 37.1 ; MS (ES+) m/z 503.9 (M + 1). Example 2.64 4V7'-Dimethoxy-indole-[2-(2-methoxyethoxy)ethyl]_2,3_dihydrospiro[吱吱和阳-迎1,4]benzodioxole Synthesis of Luyuanene-8,3,-Qiao哚]-2,(1Ή)-ketone

According to the procedure as described in Example 2, and irrelevant changes were made, using 3-(7-hydroxy-2,3-dihydro·ι,4-benzodioxanthene) _4,7_ Dimethoxy-1-0(2-decyloxyethoxy)ethyldihydro-2Η_^哚_2 ketone displaces 1-(diphenylmethyl)-3-(2-hydroxy-4-inoxyloxy) 5-methylphenylhydrazine, 3-dihydro-2-indole-2-indole-2-one, 4,7'-dimethoxy-oxime-[2_(2-methoxyethoxy)B Base]2,3 143924-sp-20091127-2 -387- 201020257 Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-&lt;哚]-2丫ΓΗ)-ketone (24%): 109-110 ° C; ^NMROOOMH^CDCls) (5 6.80 (d, J = 9.0

Hz, 1H), 6.47 (d, J = 9.0 Hz, 1H), 6.39 (s, 1H), 6.24 (s, 1H), 4.76 (ABq, 2H), 4.26-4.03 (m, 6H), 3.81 (s , 3H), 3.77-3.69 (m, 2H), 3.64-3.59 (m, 2H), 3.59 (s, 3H), 3.49-3.43 (m, 2H), 3.31 (s, 3H) ; 13C NMR (75 MHz , CDC13) &lt;5 178.4, 155.6, 150.4, 144.1, 139.7, 137.6, 131.0, 120.2, 119.5, 113.4, 111.1, 106.1, 98.7, 71.9, 69.8, 68.8, 64.5, 63.8, 59.0, 57.5, 56.4, 56.0, 41.2 ; MS (ES+) m/z 457.9 (M + 1). Example 2.65 6-[2-(2-Methoxyethoxy)ethyl]_2,2·,3,3·-tetrahydrospiro[1,4-Dioxetidene[2,3-f Synthesis of 吲哚-8,8'-furo[2,3-g][l,4]benzodioxolene]-7(6Η)-one

According to the procedure as described in Example 2, and with irrelevant changes, 8-(7-hydroxy-2,3-dihydro-l,4-benzodioxanthene-6_yl)_6_[ 2-(2-methoxyethoxy)ethyl]-2,3,6,8-tetrahydro-7Η-[1,4]dioxolynene[2,3-f]indole-7 -keto-substituted 1-(diphenylmethyl)-3-(2-hydroxy-4-indolyl-5-nonylphenyl)-l,3-dihydro-2H-indol-2-one' obtained 6 -[2-(2-methoxyethoxy)ethyl]_2,2,3,3'-tetrahydrospiro[1'4-dioxadecene-p-8,8-furan And [2,3-g][l,4]benzodioxanthene]-7(6H)-one (74%): melting point 146_148°c; 1H NMR (3〇〇MHz, CDCl3) δ 6.64 (s, 1H), 6.56 (s, 1H), 6.43 (s, 1H), 6.22 (s, 1H), 4.67 (ABq, 2H), 4.27-4.03 (m, 8H), 3.98-3.65 (m, 4H) ), 3.65-3.55 (m, 2H), 3.52-3.45 (m, 2H), 143924-sp-20091127-2 -388- 201020257 3.34 (s, 3H) ; 13C NMR (75 MHz, CDC13) &lt;5 177.6 , 155.0, 144.4, 143.8, 139.6, 138.2, 136.4, 124.7, 121.4, 113.3, 111.5, 99.3, 99.2, 80.1, 71.9, 70.4, 68.1, 64.6, 64.5, 64.1, 63, 9, 59.0, 57.8, 40.3; MS (ES+) m/z 455.9 (M + 1). Example 2.66 6'-(4-Methoxybenzyl)-2,3-dihydrospiro [[4,3_g][1,4]benzodioxolene-8,8'-[ Synthesis of 1,3]thiazolo[5,4-e;H丨哚]-7,(6Ή)-one

According to the procedure as described in Example 2, and insignificantly changing, 8-(7-hydroxy-2,3-dihydro-1,4-benzodioxanthene methoxyl group was used. )-6,8-Dihydro-7Η-[1,3&gt;- oxazolo[5,4-e]indol-7-one Substituted 1-(diphenylindenyl)-3-(2-yl-based- 4-decyloxy-5-methylphenyldihydro-2H, 丨哚_2-one, 6'-(4-methoxyindenyl)_2,3-dihydrospiro[吱喃[2 ,3_g][1,4]benzodioxanthene -8,8'-[1,3&gt;- oxazolo[5,4-eH哚]-7,(6Ή)-one (80%), Is a colorless solid: φ 'H NMR (300 MHz, CDC13) 5 8.76 (s, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.30 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 8.5 Hz, 1H), 6.88 (d, J = 8.6 Hz, 2H), 6.58 (s, 1H), 6.21 (s, 1H), 4.99 (ABq, 2H), 4.86 (ABq, 2H), 4.25- 4.04 (m, 4H), 3.79 (s, 3H); MS (ES+) m/z 473.1 (M + 1). Example 2.67 Γ-(diphenylmethyl)-6-hydroxyspiro[1-benzofuran_ Synthesis of 3,3,_吲哚]_2,(1Ή)__143924-sp-20091127-2 •389- 201020257

OH

6-(decyloxy)-rf phenylmethyl) snail u_ benzofuran _3,3|, 丨哚]_2, (ιή)_ 嗣 (0.22 g '0.44 mmol) in two gas smoldering Iodine trimethyl decane (〇 12 g, 〇61 mmol) was added to the solution in the (3 ml) solution at ambient temperature. The mixture was stirred at ambient temperature for 3 hours&apos; and concentrated in vacuo. The residue was purified by column chromatography to give a benzofuran benzoic acid _3,3,, 哚]_2, (1, 嗣 (225 g, 67%): 1η ν· (Li 2, CDC13) δ 7.46-7.25 (m, 1〇Η), 7.17-7.09 (m, 1Η), 7.08-7.02 (m, 1H), 7.02- 6.91 (m, 2H), 6.57- 637 (m, 2H), 6.32 (s, 1H), 6.24-6,2 (m, 1H), 5.70 (s, 1H), 4.85 (ABq, 2H). Example 2.68 _(Diphenylmethyl) each ( Synthesis of 2-methoxyethoxyethoxy)spiro[1-benzofuran_3,3,_吲哚]-2'(1Ή)-one

; (本methyl)_6_ via snail benzopyran-3,3,-吲嗓]·2,(γη)-_ (2.9 g 6'9 mmol) in anhydrous hydrazine, hydrazine-dimethyl Potassium carbonate (2.9 g, 21 mmol) was added to the solution in carbamide (3 mL) at ambient temperature. The mixture was stirred at ambient temperature for a few minutes and 2-bromoethyl methyl ether (1.9 g, 14 mmol) was added. The mixture was stirred under shame for 7 hours to cool it. 143924-sp-20091127-2 •390· 201020257 But it was at ambient temperature and poured into water (300 ml), causing sediment deposition. The solid was collected by filtration to give bis-(diphenylhydrazinyl)-6-(2-methoxyethoxy)spiro[l-benzofuran-3,3'-indole]-2' (1 Ή) - ketone (2,84 g, 85%) as colorless solid: 4 NMR (300 MHz, CDC13) δ 7.46-7.22 (m, 10H), 7.16-7.10 (m, 1H), 7.06 (s, 1H), 7.03-6.92 (m, 2H), 6.89-6.74 (m, 2H), 6.57-6.45 (m, 1H), 6.30-6.23 (m, 1H)' 4.85 (ABq, 2H), 3.92-3.87 (m, 2H ), 3.72-3.55 (m, 2H), 3.39 (s, 3H). Example 2.69 5-(Ethyloxy)-indole-(diphenylmethyl)spiro[i_benzofuran_3,3,_P?丨哚]_2, (ΓΗ)_ketone

According to the procedure as described in Example 2, and with irrelevant changes, 3-[5-(yloxy)-2-hydroxyphenyl]-benzoylmethyl) 4,3-dihydro-2Η_^ was used.哚_2_ ketone to replace 1-(diphenylfluorenyl)-3-(2-hydroxyindoleoxy_5_methylphenylhydrazine, 3_dihydroindole_2Η_Ρ?丨哚-2_ketone' to obtain 5_(benzyl Oxy)-Γ-(diphenylmethyl)spiro[1-benzofuran-3,3'-by-side]-2'(1Ή)-_ (88%) : iH NMR (300 MHz, CDC13) 5 7.43-7.26 (m, 15H), 7.17-7.10 (m, 1H), 7.06 (s, 1H), 7.05-6.91 (m, 2H), 6.90-6.76 (m, 2H), 6.55-6.46 (m, 1H) ), 6.30-6.23 (m, ih), 4.85 (ABq, 2H), 4.79 (s, 2H). Example 2.70 (monophenylmethyl)-5-hydroxyspiro[i_benzofuran_3,3,峋哚]_2,(1Ή)_ketone synthesis 143924-sp-20091127-2 201020257

According to the procedure as described in Example 2, 68, and with irrelevant changes, 5-(benzyloxy)-ΐ'_(diphenylfluorenyl)spiro-_benzofuran_3,3,啕哚]_2,(1Ή)_ 嗣Replacement of 6-(yloxy)4,_(diphenylmethyl)spirobenzofuran_3 3,吲哚]_ 2(1 ugly)-ketone' to obtain 1' kernel Benzyl)_5_ via snail [1_benzofuran_3,3,_|^哚]_ 2 (1 Η)-_ (78%), as a colorless solid: 1 η NMR (300 MHz, CDC13 ) 5 8.22 (br s, 1H), 7.30-7.08 (m, 10H), 7.02-6.93 (m, 1H), 6.88 (s, 1H), 6.85-6.75 (m, 2H), 6.65-6.49 (m, 2H), 6.38-6.26 (m, 1H), 6.13-6.02 (m, 1H), 4.65 (ABq, 2H) ° Example 2.71 Γ-(diphenylfluorenyl)-5-(2-decyloxyethoxy) Synthesis of spirobenzofuran_3,3,啕哚]_ 2'(ΓΗ)-ketone

I

According to the procedure as described in Example 2.68, and the insignificant change was made, 1 phenylmethyl) _5_ via snail [ι_benzofuran _3,3Lp 哚]_2, (1 Ή) ketone was substituted 1 -(Phenylphenyl)_6_ via snail [μbenzopyrano_3 3, _10]_2, (1Ή)-one, 1-(diphenylmethyl)-5-(2-oxime) Oxyethoxy ethoxy) snail tl_benzofuran _3 3, 吲哚]_ 2 (1 H)-one (90%), colorless solid: 1H NMR (3 〇〇 MHz, CDCl3) occupies 7 143924 -sp-20091127-2 -392- 201020257 7.25 (m, 10H), 7.15-7.07 (m, 1H), 7.04 (s, 1H), 7.00-6.90 (m, 2H), 6.58-6.44 (m, 3H) , 6.41-6.33 (m, 1H), 4.86 (ABq, 2H), 4.15-3.98 (m, 2H), 3.75-3.66 (m, 2H), 3.41 (s, 3H). Example 2.72 Γ-(Diphenylmethyl)-2,3-dihydrospiro[吱,[2,3-phan[1,4]benzodioxolene-7,3.卜来]-2'(1Ή)-_ Synthesis

1-(Diphenylfluorenyl)-3-(5-hydroxy-2,3-dihydro-1,4-benzodioxan) was used according to the procedure described in Example 2, and the insignificant changes were applied. 1,3-dihydro-2-indole-2-one substituted 1-(diphenylmethyl)-3-(2-hydroxy-4-methoxy-5-nonylphenyl) )-1,3-dihydro-2Η-4丨ρ-butan-2-one, obtaining Γ-(diphenylmethyl)_2,3-dihydrospiro[bit, benzo[2,3-;Q[l, 4] benzodioxantemene _7,3,_吲哚]-2,(1Ή)-one (85%), as a colorless solid: iHNMROOOMHz 'DMSO^) (5 7.47-7.22 (m, gin 12H) ), 7.10 (ddd, J = 7.8, 7.8, 1.2 Hz, 1H), 6.99 (dd, J = 7.4, 7.4 Hz, 1H), 6.88 (s, 1H), 6.58 (d, J = 7.8 Hz, 1H) , 6.32 (d, J = 8.3 Hz, 1H), 6.04 (d, J = 8.3 Hz, 1H), 4.93 (d, J = 9.5 Hz, 1H), 4.81 (d, J = 9.5 Hz, 1H), 4.27 (s, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.8, 148.8, 144.7, 142.0, 137.6, 137.5, 131.6, 129.3, 128.7, 128.5, 128.3, 128.1, 127.9, 127.7, 127.6, 123.9, 122.9 , 122.4, 113.8, 111.0, 109.9, 80.1, 64.1, 63.9, 58.1, 57.1; MS (ES+) m/z 461.9 (M + l). Example 2.73 143924-sp-20091127-2 -393 - 201020257 1'-( two Benzyl)-4|,6'-dimethoxy-2,3-dihydrospiro[吱,[2,3-8][1,4]benzodioxene-8,3 '-啕哚]-2'(rH)-S

Following the procedure as described in Example 2, and applying an insignificant change, 1-(1 thiol)-3-(7-carbyl-2,3-diaza-1,4-benzodioxane was used.圜6_6_dimethoxy-1,3-dihydro-2H-indol-2-one replacing 1-(diphenylfluorenyl)-3-(2-hydroxy-4) -decyloxy-5-methylphenyl)-l,3-dihydro-2H-indol-2-one, obtaining Γ-(di-methyl)-4,6-monomethoxy-2, 3-dihydrospiro[吱η南和[2,3_g][i,4]benzodioxanthene-8,3'-noise]-2'(1Ή)-one (96%), Colorless solid: ^ NMR (300 MHz, CDC13) 5 7.41-7.24 (m, 10H), 6.97 (s, 1H), 6.42 (s, 1H), 6.19 (s, 1H), 6.04 (d, J = 1.8 Hz , 1H), 5.69 (d, J = 1.8 Hz, 1H), 4.81 (ABq, 2H), 4.21-4.06 (m, 4H), 3.62 (s, 3H), 3.47 (s, 3H) ; MS (ES+) m/z 522.1 (M + 1). Example 2.74 - Synthesis of (a succinyl) snail [吱, [[2,3_g] 噚 噚 _8,3,•吲哚]_2Ι(1Ή) ketone

Follow the procedure as described in Example 2.40 and perform irrelevant changes

143924-SP-20091127-2 •394· 201020257 吲哚-3-yl]benzonitrile to obtain 1'-(diphenylmethyl)spiro[P-aramid[2,3-g]quinoxaline-8 ,3·-叼| 哚]-2'(1Ή)-ketone (34%) : 1H NMR (300 MHz, CDC13) 5 8.57 (d, J = 1.5 Hz, 1H), 8.46 (d, J = 1.5 Hz , 1H), 8.07-8.04 (m, 1H), 7.63-6.86 (m, 15H), 6.55-6.52 (1^1H), 5,10 (ABq, 2H). Example 3 Synthesis of 6-decyloxy-5-methylspiro[1- benzofuran-3,3'-fluorene]-2'(1Ή)-one

Γ-(Diphenylmethyl)-6-decyloxy-5-mercaptospiro[1-benzofuran-3,3·-啕哚]-2'(1Ή)-one (7.2 g ' 16.1 mM A stirred solution of triethyl decane (15 ml) and trifluoroacetic acid (50 ml) was refluxed for 14 hours. The solution was concentrated in vacuo and precipitated with methylene chloride to give 6-methoxy-5-methylspiro[l-benzofuran-3,3'-indole]-2 (1)-one (3.9) Gram, 86%), as colorless solid: mp. &lt;250 °C; 1H NMR (300 MHz, DMSO-d6) δ 10.54 (s, 1H), 7.23-7.14 (m, 1H), 7.03 (d, J = 6.9 Hz, 1H), 6.95-6.86 (m, 2H), 6.58 (s, 1H), 6.41 (s, 1H), 4.68 (ABq, ❹ 2H), 3.73 (s, 3H), 1.91 (s, 3H) 13C NMR (75 MHz, DMSO-dg) &lt;5 179.2, 160.4, 158.9, 142.2, 133.4, 129.1, 124.4, 124.2, 122.7, 120.3, 118.5, 110.2, 94.3, 80.1, 58.0, 56.0, 16.0; MS ( ES+) m/z 282.2 (M + 1). Example 3.1 Synthesis of 4'-Chloro-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,anthracene-2'(1Ή)-one

143924-sp-20091127-2 -395- 201020257 Following the procedure as described in Example 3, and applying an insignificant change, using 1'-(diphenylmethyl-M'-carbyl-5,6-dihydrospiro [Benzo[1,2-b : 5,4-b']difuran-3,3'-啕哚]-2'(1Ή)- Brewing I Substituting Γ-(Diphenylmethyl)_6_Methoxy _5_methylspiro-fl_benzofuran-3,3'-啕哚]-indole)-one, obtaining 4,-carbyl-5,6-dihydrospiro[benzo[l,2-b : 5,4 7']difuran-3,3·-吲哚]_2,(1Ή)-one (70%), as a colorless solid:

Melting point &gt; 200 ° C ; 1H NMR (300 MHz, DMSO-d6) 5 10.80 (s, 1 Η), 7.23 (dd, J = 8.0, 8.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H) , 6.87 (d, J = 7.7 Hz, 1H), 6.49 (s, 1H), 6.31 (s, 1H), 4.84 (d, J = 9.6 Hz, 1H), 4.68 (d, J = 9.6 Hz, 1H) , 4.46 (t, J = 8.7, Hz, 2H), 2.92 (t, J = 8.6 Hz, 2H) ; 13 C NMR (75 MHz, DMSO-d6) δ # 182.8, 166.0, 165.8, 148.3, 134.9, 134.3 , 133.8, 127.1, 123.9, 123.2, 122.4, 113.4, 96.5, 81.8, 76.6, 62.4, 32.9; MS (ES+) m/z 313.9 (M + 1), 315.9 (M + 1). Example 3.2 Synthesis of 6-bromospiro[1-benzofuran_3,3,_吲哚]_21 (1 ketone-ketone)

According to the procedure as described in Example 3, and the insignificant change was made, 6-glycosyl-indole-(diphenylfluorenyl) screw-benzofuran_3,3,_峋哚]_2, (1Ή) was used. __Replacement of Γ-(diphenylmethyl)-6-methoxy_5-fluorenyl snail [i_benzofuran_3,3l 哚 哚]_ 2'(1Ή)-ketone' to obtain 6-bromo Base snail [1_benzofuran_3,3,-4哚]-2,(1Ή)-one (89%), as colorless solid: MS (ES+) m/z 316.1 (Μ + 1), 318.1 CM + 1). Example 3.3 Synthesis of 5,6-dimethylspiro[1-benzofuran_3,3,_吲哚]_2,(1Ή)-one 143924-sp-20091127-2 •396- 201020257

According to the procedure as described in Example 3, and the insignificant change was made, 1-(monophenylmethyl)-5,6-dimethylspiro[1-benzopyrano_3,3'-啕哚 was used. ]-2'(1Ή)-ketone replacement Γ-(diphenylmethyl)-6-methoxy-5-methylspiro[μbenzofuran_3,3,_吲嗓]-2'(1Ή) -ketone' obtains 5,6-dimethylspiro[1-benzoxazole»3,3'·decaine-2,(1Ή)-one (88%) as a colorless solid: melting point 206_207° c (ethyl acetate/hexane); lH NMR (300 MHz, DMSO-d6) δ 10.5 (s, 1 Η), 7.23-7.18 (m, 1H), 7.03-7.01 (m, 1H), 6.94-6.88 ( m, 2H), 6.73 (s, 1H), 6.43 (s, 1H), 4.68 (ABq, 2H), 2.13 (s, 3H), 1.99 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 178,9, 159.1, 142.2, 138.0, 133.3, 129.1, 127.0, 124.2, 124.1, 122.7, 111.2, 110.2, 79.5, 58.2, 20.2, 19.1; MS (ES+) m/z 266.3 (M+l). Example 3.4 5'-Fluoro-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-吲哚]-2, (1Ή)_ Ketone synthesis

According to the procedure as described in Example 3, and irrelevant changes were made, using 1(diphenylindenyl)-5.-fluoro-5,6-dihydrospiro[benzo[l,2-b:5] ,4-b,]difuran-3,3·-啕哚]-Τ(ΓΗ)-嗣substituted 1·-(diphenylmethyl)_6_methoxy_5-fluorenylspiro[1-benzo Furan-3,3'-indole]-2'(1Ή)-one, 5'-fluoro-5,6-dihydrospiro[benzo[l,2-b:5,4-b'] Difuran-3,3'-indole]-2'(1Ή)-one (91%) as colorless solid: m.p. 257-259°C (diethyl ether); 1H NMR (300 MHz, CDC13) 5 10.35 (s ,1Η), 143924-sp-20091127-2 -397- 201020257 6.86-6.73 (m, 3H), 6.43 (s, 1H), 6.22 (s, 1H), 4.64 (ABq, 2H), 4.43 (t, J = 9.0 Hz, 2H), 2.93-2.90 (m, 2H); MS (ES+) m/z 298.0 (M + 1). Example 3.5 Synthesis of 6'-fluoro-5,6-dihydrospiro[benzo[nb:5,4_b,]difuran-3,3,_呻哚]_2, (i'h)-one

According to the procedure as described in Example 3, and with irrelevant changes, use 1'-(diphenylmethyl)-6'-free radical-5,6-dihydrospiro[benzo[l,2-b : 5,4-b,]difuran-3,3'-Mb]-2·(1Ή&gt;ketone replacement ι'_(diphenylfluorenyl)_6_methoxy_5_methylspirobenzene And furan-3,3'-吲哚]-2'(1'11)-one to obtain 6,-fluoro-5,6-dihydrospiro[benzo[l,2-b: 5,4- b·]difuran-3,3'-indole]-2'(1Ή)-one (71%) as colorless solid: mp 249-251°C (diethyl ether); 4 NMR (300 MHz, DMSO-d6 5 10.74 (s, 1H), 7.18-7.13 (m, 1H), 6.79-6.42 (m, 2H), 6.55 (s, 1H), 6.42 (s, 1H), 4.74 (ABq, 2H), 4.52 ( t, J = 9.0 Hz, 2H), 2.99 (t, J = 9.0 Hz, 2H); MS (ES+) m/z 298.0 (M + 1). Example 3.6 3-曱-based snail [pfuming and [3] ,2-f][l,2]Benzene is different from the number of e sitting _5,3'_Ρξ丨嗓]

In the case of l'-(4-methoxyindolyl)-3-methylspiro[. Sit-5,3'-叼丨哚]-2'(1Ή)-one (3.00 g, 7.76 mmol) in di-methane (2 mL) -398 - 143924-sp-20091127-2 (S) To the stirred solution of trifluoroacetic acid (20 ml) was added trifluorodecane acid (6.8 mL, 76.8 mmol). The reaction mixture was stirred at ambient temperature for 22 hours&apos; and concentrated in vacuo. The residue was basified with a saturated sodium hydrogen carbonate solution and extracted with ethyl acetate. The combined organic solution was washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography using ethyl acetate (yield: 30% to &lt;RTI ID=0.0&gt;&gt; Benzoisoxazole-5,3'-(9)哚]-2'(1Ή)-one (1.72 g, 76%): mp 226-227. (:(ethyl acetate ® / hexane); 1H NMR (300 MHz, DMSO-d6) 5 10.82 (s, 1 Η), 7.69 (d, J = 9.0

Hz, 1H), 7.27 (m, 1H), 7.11-7.04 (m, 2H), 6.97-6.90 (m, 2H), 4.89 (AB, 2H), 2.40 (s, 3H) ; MS (ES+) m/ z 292.9 (M + 1) ° Example 3.7 5-Alkyl-6-methoxyspiro[1-Benzium σ南_3,3'_p"丨嗓]_2'(1'h)-ketone synthesis

K Φ Γ-(diphenylfluorenyl)-5-fluoro-6-methoxyspiro[1-benzofuran-3,3 was used according to the procedure as described in Example 3, and irrelevant changes were applied. ,-吲哚]-2'(1Ή)-ketone replacement Γ-(diphenylfluorenyl)_6_methoxy_5_methylspiro[μbenzofuran-3Χ嗓]-2·(1Ή)-one 'Available 5-fluoro-6-methoxyspiro[1-benzofuran-3,3,-indole]-2'(1Ή)-one (82%) ' is a colorless solid: mp 222-225 C ; 1H NMR (300 MHz, CDC13) δ 8.33 (s, 1 Η), 7.29-7.21 (m, 1H), 7.12 (d, J = 6.7 Hz, 1H), 7.03 (ddd, J = 7.5, 7.5, 0.9 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.59 (d, J = 6.8 Hz, 1H), 6.52 (d, J = 10.1 Hz, 1H), 4.96 (d, J = 9.1 Hz, 1H), 4.68 (d, J = 9.1 Hz, 1H), 3.85 (s, 3H); 13 C NMR (75 MHz, CDC13) δ 179.9, 157.2, 149.3, 143924-sp-20091127-2 201020257 149.1 (d, J = 12.4 Hz), 146.1, 140.2, 132.2, 129.1, 123.8 (d, J = 42.8 Hz), 118.6 (d, J = 7.1 Hz), 110.7, 110.4, 96.3, 80.5, 58.6, 56.4 ; MS (ES+) m/z 286.2 (M + 1). Example 3.8 Synthesis of 5-fluoro-spiro[1-benzofuran-3,3'-吲哚]-2'(1Ή)-copper

1 1'-(Diphenylmethyl)-5-1 snail [1-benzofuran_3,3,_p5丨哚]- was used according to the procedure as described in Example 3, and with irrelevant changes. 2'(1Ή)-ketone replacement Γ-(diphenylfluorenyl)-6-methoxy-5-mercaptospiro[1-benzofuran_3,3,_啕哚]-2'(1Ή)- Ketone 'obtained 5-fluoro-spiro[1-benzofuran_3,3,_ρ哚哚]_2, (1, India__ (87%): melting point 224-226C; 4 NMR (300 MHz, DMSO-d6 ) (5 10.65 (s, 1Η), 7.23 (ddd, J = 7.7, 7.7, 0.9 Hz, 1H), 7.09 (d, J = 7.0 Hz, 1H), 7.06-6.87 (m, 4H), 6.58 (dd , J = 8.0, 2.7 Hz, 1H), 4.80 (d, J = 9.3 Hz, 1H), 4.67 (d, J = 9.3 Hz, 1H) , 13C NMR (75 MHz, DMSO-c^) &lt;5 178.2 , 158.9, 157.1, 142.3, 132.4, 131.3, 131.1, 129.5, 124.3, 122.8, 116.5, 116.2, 111.0, 110.9, 110.7, 110.4, 80.2' 58.4, MS (ES+) m/z 260.0 (M + 1). 3.9 Synthesis of 6-methoxyspiro[1-benzofuran_3,3,啕哚]_2,(1Ή) ketone

·-吲哚]-2'(1Ή)-ketone 143924-sp-20091127-2 using Γ-(二201020257 displacing 1-(diphenylmethyl)_6-methoxy-5-methylspiro[ι_benzene And furan_3,3,_吲哚]_ 2(111)-ketone' obtains 6-methoxyspiro[1_benzofuran_3,3,_1^哚]_2, (1,11)-one (98%) ' is a colorless solid: iHNMR (300MHz, CDC13) 6 8.23-8.11 (br,1H), 7.30-6.90 (m, 4H), 6.69 (d, J = 8.4 Hz, 1H), 6.54 (d, J = 2.4 Hz, 1H), 6.39 (dd, J = 8.4, 1.8 Hz, 1H), 4.98 (d, J = 9.0 Hz, 1H), 4.71 (d, J = 9.0 Hz, 1H), 3.78 (s, 3H) ; MS (ES+) m/z 268.3 (M + 1). Example 3.10 2'3-Dihydrospich-[2,3-g][l,4]benzodioxolene _ 8,3,_byside]_2'(ΓΗ)_ ketone synthesis

According to the procedure as described in Example 3, and the insignificant change was made, 1'-(diphenylmethyl)-2,3-dihydrospiro[2,3-g][l,4 Benzodioxanthene-8,3·-吲哚]-2'(1Ή)-ketone replacement Γ-(diphenylfluorenyl)·6_methoxy_5_methylspiro[1-benzene And furan-3J-吲哚]-2'(1Ή)-one, to obtain 2,3-dihydrospiro [bito-and-[2,3-g] [1,4] benzodioxanthene-8 , 3'-吲哚]-2,(1Ή)-one (89%), as colorless solid: mp. &lt;250°C (diethyl ether); 4 NMR (300 MHz, DMSO-d6) &lt;5 10.57 (s ,1Η), 7.24 (ddd, J = 7.7,7.7,1.0 Hz, 1H), 7.09 (d, J = 6.9 Hz, 1H), 6.96 (dd, J = 7.5, 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.16 (s, 1H), 4.73 (d, J = 9.2 Hz, 1H), 4.60 (d, J = 9.2 Hz, 1H), 4.20-4.15 ( m, 2H), 4.13-4.08 (m, 2H); 13C NMR (75 MHz, DMSO-d6) &lt;5 178.3, 154.6, 144.0, 141.7, 137.7, 132.5, 128.7, 123.7, 122.2, 121.4, 111.1, 109.8 , 98.6, 79.4, 64.2, 63.6, 57.6; MS (ES+) m/z 296.3 (M + 1). Example 3.11 143924-sp-20091127-2 -401 - 201020257 3,4-Dihydro-211-spiro [bito-and-[2,3-11][1,5]benzodiazepine-decenene-9, Synthesis of 3'-啕哚]-2'(1Ή)-ketone

Ν Η According to the procedure as described in Example 3, and performing irrelevant changes, use 1'-(diphenylhydrazinyl)-3,4-dihydro-2Η-spiro[吱,[2,3-h ][l,5]benzo-dioxazaeptenene-9,3'-啕哚]-2'(1Ή)-one substituted Γ-(diphenylmethyl)_6_曱oxy-5-曱Base snail [1-benzopyran-3,3'-吲嗓]-2'(1Ή)-drying, obtaining 3,4-dihydro-2Η-spiro [biting and [2,3-h][ l,5]benzodioxanthylenes9,3,-anthracene-2,(1Ή)-one (70%), colorless solid: melting point 235-236 ° C (sterol); 1H NMR (300 MHz, DMSO-d6) δ 10.60 (s, 1 Η), 7.24 (dd, J = 7.8, 7.2 Hz, 1H), 7.11 (d, J = 7.2 Hz, 1H), 6.97 (dd, J = 7.8 , 7.5 Hz, 1H), 6.92 (d, J = 7.8 Hz, 1H), 6.58 (s, 1H), 6.27 (s, 1H), 4.78 (d, J = 9.3 Hz, 1H), 4.65 (d, J = 9.3 Hz, 1H), 4.14-4.01 (m, 2H), 3.98-3.87 (m, 2H), 2.06-1.97 (m, 2H); 13 C NMR (75 MHz, DMSO-d6) δ 178.2, 156.3, 152.5, 145.8, 141.8, 132.4, 128.8, 123.8, 123.7, 122.3, 115.6, 109.8, 103.0, 79.8, 70.7, 57.6, 31.9; MS (ES+) m/z 310.0 (M + 1). Example 3.12 Synthesis of 2-methylspiro[吱,[2,3-f)[l,3]benzo-P-azole _7,3,_吲哚]_2,(1Ή) ketone

According to the procedure as described in Example 3, and the insignificant changes were made, Γ-(diphenylmethyl)_2-methylspiro was used and [2,3 phantom [13] benzoxazole was used.

143924-sp-20091127-2 -402· 201020257 -3-3,3'-令朵]-2|(1Ή)-ketone' obtains 2-mercapto snail [吱,[2,3_耶,3]benzene And hehe. -7,3'-吲哚]-2'(1Ή)-one (62%) was obtained as a colorless solid: m.p. 242. (3 (diethyl ether); 1H NMR (300 MHz, CDC13) 6 8.20 (br s, 1 Η), 7.36 (d, J = 8.7 Ηζ, 1H), 7.30-7.24 (m, 1H), 7.08 (d, J = 7.5 Hz, 1H), 7.00 (d, J = 8.7 Hz, 1H), 6.99-6.93 (m, 1H), 6.96 (d, J = 7.8 Hz, 1H), 5.96 (d, J = 6.0 Hz, 1H) , 5.42 (d, J = 5.0 Hz, 1H), 2.41 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 176.2, 165.2, 151.4, 146.1, 142.0, 138.2, 130.6, 130.1, 125.0, 123.1, 114.3, 111.5, 110.9, 88.4, 76.3,14,6 ; MS (ES+) m/z 331.1 (M + 39). ® Example 3.13 3-Methyl snail [biting [[2,3-f][l, 3] Synthesis of benzoxazole-7,3,_吲哚]_2,2,(1Ή,3Η)_dione

According to the procedure as described in Example 3, and with irrelevant changes, Γ-(diphenylhydrazinyl)-3-methylspiro[N-[2,3-f][l,3]benzo Oxazole-7,3W| ® 哚]-2,2'(1Ή,3Η)-dione replacement 1\diphenylmethyl)_6-methoxy-5-methylspiro[1-benzofuran-3 , 3'-吲哚]-2'(1Ή)-ketone, obtain 3-methylspiro [snolo[2,3-f][l,3]benzoxazole-7,3'-M丨哚]-2,2|(1Ή,3Η)-dione (88%) as colorless solid: mp. &lt;250°C (diethyl ether); 4 NMR (300 MHz, DMSO-dg) &lt;5 10.64 (br s,1Η), 7.30-7.22 (m, 1H), 7.09 (d, J = 7.0 Hz, 1H), 7.01-6.90 (m, 3H), 6.75 (s, 1H), 4.82 (d, J = 9.3 Hz , 1H), 4.70 (d, J = 9.3 Hz, 1H), 3.30 (s, 3H); 13 C NMR (75 MHz, DMSO-d6) δ 178.2, 157.0, 154.5, 141.8, 136.2, 132.8, 132.4, 128.9 , 123.8, 122.3, 122.0, 109.9, 104.9, 92.3, 79.8, 57.8, 28.2; MS (ES+) m/z 309.1 143924-sp-20091127-2 -403-201020257 (Μ+l). Example 3.14 Synthesis of 1-methylspiro[N-and-[3,2_ye,3]benzoxazole-7,3Wbdu]-2,2'(1Η,1Ή)^_

According to the procedure as described in Example 3, and the insignificant change was made, 1'-(diphenylhydrazinyl) small methyl snail [M-benzo[3 2_η[13]benzoxazole_7,3, _^ 哚]-2,2·(1Η,1Ή)-dione replacement 1, _(diphenylmethyl)_6_methoxy_5_methylspiro[]L benzofuran-3,3· -峋哚]-2'(1Ή)-ketone, 1,1(diphenylmethyl)4_methylspiro[吱,[3,2-f][l,3]benzoxazole_7 , 3,-4丨哚]_2,2,(1Η,ΓΗ)-·τι ketone (53%), as colorless solid: melting point &gt;250. (:(methanol); 1 η NMR (300 MHz, DMSO-dg) &lt;5 10.69 (br s, 1H), 7.30-7.25 (m, 1H), 7.14-7.08 (m, 2H), 7.01-6.92 ( m, 2H), 6.69 (s,

1H), 4.82 (d, J = 9.3 Hz, 1H), 4.70 (d, J = 9.3 Hz, 1H), 3.20 (s, 3H); 13 C NMR (75 MHz 'DMSO-d6) &lt;5 178.2, 156.1, 154.2, 142.5, 141.9, 132.4, 128.9' 126.0' 124.0, 122.4, 109.9, 104.0, 93.9, 79.8, 57.8, 28.1 ; MS (ES+) m/z 308.9 (M + 1) 〇® Example 3.15 7 gas base Synthesis of 5,6-monohydrospiro[benzophenanthrene succinate: 5,4,7]difuran-3,3,anthracene

According to the procedure as described in Example 3, and irrelevant changes were made, 143924-sp-20091127-2 (S) ► 404- 201020257 using 7-yl-1-(diphenylmethyl)-3-(6) -hydroxy-2,3-dihydro-1-benzofuran-5-yl H,3-dihydro-2H,anthracene-2-one substituted Γ-(diphenylmethyl)-6-methoxy-5 - mercaptospiro[1-benzofuran-3,3'-indole]-2'(1?)-one, which gives 7-chloro-5,6-dihydrospiro[benzo[l,2- b: 5,4-b1]difuran-3,3·-吲哚]-2·(1Ή)-_ (78%), as colorless solid: melting point &gt;250°C (diethyl ether); 4 NMR (300 MHz, DMSO-d6) &lt;5 11.01 (s,1Η), 7.30 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 7.1 Hz, 1H), 7.00-6.94 (m, 1H), 6.56 (s, 1H), 6.40 (s, 1H), 4.80 (d, J = 9.4 Hz, 1H), 4.68 (d, J = 9.4 Hz, 1H), 4.49 (m, 2H), 2.95 (m, 2H) 13 C NMR (75 MHz, DMSO-d6) δ 178.5, 161.0, 160.5, © 139.4, 134.7, 128.4, 123.4, 122.3, 120.1, 119.8, 118.9, 113.8, 92.3, 79.8, 72.0, 58.0, 28.2 ; MS ( ES+)m/z 313.7 (M+1), 315.7 (M+l). Example 3.16 7'-Fluoro-5,6-dihydrospiro[benzo[l,2-b: 5,47'] Synthesis of ketone-2,3'-嘀嗓]-2,(1Ή)-ketone

77-Fluoro-1-(diphenylmethyl)-3-(6-hydroxy-2,3-dihydro-1-benzene) was used according to the procedure described in Example 3, and insignificantly changed. And furan-5-yl)-1,3-dihydro-2Η-indol-2-one substituted Γ-(diphenylfluorenyl)_6_methoxy_5-fluorenyl snail [ι_benzofuran-3 , 3'-吲哚]-2' (ΓΗ&gt; ketone, obtaining 71-fluoro-5,6-dihydrospiro[p, and [l,2-b: 5,4-b']difuran-3, 3W丨哚]-2,(1Ή)-_ (97%), as colorless solid: mp. &lt;250°C (diethyl ether); 4 NMR (300 MHz, DMSO-d6) 5 11.01 (s, 1 Η), 7.30 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 7.1 Hz, 1H), 7.00-6.94 (m, 1H), 6.56 (s, 1H), 6.40 (s, 1H), 4.80 (d, J = 9.4 Hz, 1H), 4.68 (d, J = 9.4 Hz, 1H), 4.49 (m, 143924-sp-20091127-2 • 405- 201020257 2H), 2.95 (m, 2H) ; 13 C NMR (75 MHz, DMSO-d6) ¢5 178.5,161.0, 160.5, 139.4, 134.7, 128.4, 123.4, 122.3, 120.1, 119.8,118.9, 113.8, 92.3, 79.8, 72.0, 58.0, 28.2 ; MS (ES+) m/z 298.0 (M + 1). Example 3.17 4'-Fluoro Imethyl-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3W丨哚] -2'(1Ή)-ketone synthesis

According to the procedure as described in Example 3, and with insignificant changes, use 1'-(diphenylfluorenyl) flufen-7'-methyl-5,6-dihydrospiro[benzo[l, 2-b : 5,4-b,] Difuran-3,3'-吲哚]-2\1Ή)-one substituted Γ-(diphenylfluorenyl)-6-decyloxy-5-fluorenyl snail [1-benzofuranium]-2'(1Ή)-_, 4'-fluoro-7'-methyl-5,6-dihydrospiro[benzo[l,2-b: 5,4 -b,]difuran-3,3,-anthracene-2,(1Ή)-one (76%) as colorless solid: mp. &lt;250°C (diethyl ether); 1H NMR (300 MHz, DMSO- D6) (5 10.84 (s, 1H), 7.12-7.07 (m, 1H), 6.72-6.65 (m, 1H), 6.59 (s, 1H), 6.37 (s, 1H), 4.78-4.73 (m, 2H ), 4.50 (t, J = 8.7 Hz, 2H), 2.97 (d, J = 8.7 Hz, 2H), 2.20 (s, φ 3H) ; MS (ES+) m/z 311.9 (M + 1). Example 3.18 Synthesis of 6-hydroxyspiro[1-benzofuran-3,啕哚]-2'(1Ή)-_

ΟΗ 苄 benzyloxyindole '-(diphenylfluorenyl) snail [1·benzofuran-3,3'-吲哚]-2'(1Ή)-one (0·60 g, 1.2 mmol) The suspension in methanol (20 ml) was degassed by bubbling nitrogen 143924-sp-20091127-2 -406- (S) 201020257 over 1 hour, then adding palladium hydroxide/carbon (2%, 0.08 g '0.12 mmol). The mixture was spoiled at 60 ° C for 16 hours under 120 psi of hydrogen. The mixture was filtered through a pad of celite, and concentrated to dryness in vacuo. The residue obtained was recrystallized from ethyl acetate and hexane to give 6-bromo-2H-spiro[benzofuran_3,3, · Dihydrotetrazol] _2, ketone (25 g, 83%), as a colorless solid: iHNMR (300 MHz, DMSO-d6) ό 10.86-9.35 (br, 2H), 7.19 (td, J = 7.6, 1.2 Hz, 1H), 7.03 (d, J = 73 Hz, 1H), 6.96-6.84 (m, 2H), 6.42 (d, J = 8.2 Hz, 1H), 6.29 (d, J = 2.1 Hz, 1H), 6.17 (dd, J = 8.2, 2.1 Hz, 1H), 4.72 (d, J = ® 9·2 Hz, 1H), 4.59 (d, J = 9,2 Hz, lii) ; MS (ES+) m/z 254.1 (M + 1). Example 3.19 (3S)-3-{[l'-(Diphenylfluorenyl)_2l keto-r,2,-dihydrospirobenzofuran_3,3, 丨嗓]-6-yl]oxy Synthesis of tetrahydropyrrole small carboxylic acid tert-butyl ester

CH CH〇Ο at 0 ° C, in Γ-(diphenylmethyl)-6-hydroxyspiro-U-benzofuran _3, 吲哚]_ 2, (10)-keto-gram '1Ό7 mol), (10) Each of the perylene-tetrachloropyrene-dicarboxylic acid tri-butyl ester (0.60 g, 3.22 mmol) and triphenylphosphine (〇.7 g, 2 mmol) in tetrahydrofuran (50 ml) Inside, slowly add azodicarboxylic acid diethyl acetonate (0,423⁄4 liters, 2.68 millimoles). The compound was allowed to stand at ambient temperature for 16 hours and then concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate/hexane-1:2) to give (3S) of each of {[1, _(diphenylmethyl)-2, quinone dihydrospiro-benzene And furan-3,3·-,5-mercapto]oxy}tetrahydropyrrole small carboxylic acid III 143924-sp-20091127-2 -407- 201020257 ester, oil (0.52 g, 83%): 1H NMR (300 MHz, CDC13) δ 7.43-7.25 (m, 10H), 7.16-7.06 (m, 1H), 7.07-6.91 (m, 3H), 6.58-6.43 (m, 3H), 6·38-6 ·25 (m, 1H), 5.00 (d, J = 9.0 Hz, 1H), 4.80 (s, 1H), 4.73 (d, J = 9.0 Hz, 1H), 3.65-3.36 (m, 4H), 2.22- 1.95 (m, 2H), 1.45 (s, 9H); MS (ES+) m/z 611.3 (M + 23). Example 3.20 (3S)-3-[(2'-keto-oxime, 2'-dihydrospiro[1- benzofuran-3,3'-indolyl]-6-yl)oxy]tetrahydropyrrole Synthesis of 1-carboxylic acid tert-butyl ester

(3S)-3-{[r-(Diphenylmethyl)-2'-keto-oxime, 2·-dihydrospiro[1-benzofuran-3,3·-啕哚]-6-yl a suspension of tetrakis-butyl ester of tetrahydropyrrole-1-carboxylic acid (〇5 g, 0.85 mmol) in decyl alcohol (20 ml) was passed through a stream of nitrogen After degassing for an hour, then palladium hydroxide on carbon (20%, 0.084 g) was added. The mixture was stirred at 60 ° C for 48 hours under 120 psi of hydrogen. The mixture was filtered through a pad of celite and the filtrate was concentrated in vacuo. The residue obtained is recrystallized from ethyl acetate and hexane to give (3S)-3-[(2,-keto-indole, 2,-dihydrospiro[1-benzofuran-3,3 '-吲哚]-6-yl)oxy]tetrahydropyrrole-1-carboxylic acid tert-butyl ester (0.25 g, 70%) ' is a colorless solid: 1H NMR (300 MHz, CDC13) 6 8.01 (br s,1Η), 7.29-7.09 (m, 1H), 7.12 (d, J = 7.0 Hz, 1H), 7.02 (dd, J = 7.5, 0.8 Hz, 1H), 6.92 (d, J = 7.7 Hz, 1H ), 6.66 (d, J = 8.3 Hz, 1H), 6.47 (d, J = 2.1 Hz, 1H), 6.33 (dd, J = 8.3, 2.1 Hz, 1H), 4.96 (d, J = 9.1 Hz, 1H ), 4.81 (s, 1H), 4.69 (d, J = 9.1 Hz, 1H), 3.64-3.37 (m, 4H), 2.22-1.96 (m, 2H), 1.45 (s, 9H) ; MS (ES+) 143924-sp-20091127-2 -408- 201020257 m/z 445.0 (Μ + 23) 〇 Example 3.21 6,7-Dihydrogen lysine and kiss bite _3,3, _(4)] Synthesis Η 1 -( -N-methyl)-6,7-dihydro-5Η-spiro[吱,[3,2 克克克_3,3,_十朵]· 2'(1Ή)-嗣(0.61g, 132 units A solution of diethyl decane (0.67 mL, 4.2 mmol) in trifluoroacetic acid (4.5 mL) was stirred under reflux and nitrogen for 2.5 h. Upon cooling, the reaction was diluted with water (4 mL) and ethyl acetate (3.times.25 mL). The combined organic solution was washed with brine (50 ml), dried over sodium sulfate. The residue was dissolved in dichloromethane (1% EtOAc) (5 mL). This material was collected by filtration' and washed with hexane. Drying under air to provide 6,7-dihydro-511_spiro[吱,[3,2-g] octa--3,3'-W 哚]-2'(1Ή)-one (0.25 g, 63%), a colorless solid body. Another (0. 丨 4 g '37%) product was also recovered by way of making the filtrate

Concentrated and the residual solid was triturated with hexane: mp 216-220. (: (hexane); iH NMR (300 MHz, DMSO-d6) δ 10.58 (s, 1 Η), 7.23 (ddd, J = 7.8, 7.5, 0.9 Hz, 1H), 7.08 (d, J = 7.2 Hz, 1H), 6.98-6.91 (m, 2H), 6.36 (s, 1H), 6.31 (s, 1H), 4.74 (d, J = 9.0 Hz, 1H), 4.61 (d, J = 9.0 Hz, 1H), 4.05 (dd, J = 5.1, 4.8 Hz, 2H), 2.61-2.45 (m, 2H), 1.84-1.77 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 178.6, 159.5, 155.4, 141.8 , 132.9, 128.6, 123.8, 123.6, 122.3, 121.4, 114.8, 109.7, 97.9, 79.5, 66.0, 57.3, 23.9, 21.7; MS (ES+) m/z 294.1 (M + 1). 143924-sp-20091127-2 -409· 201020257 Example 3.22 1-Methyl-1H-spiro[吱,[3,2-g][l,4]benzoindole_8,3,_10]_2,2·(1Ή, 3Η)-dione synthesis

According to the procedure as described in Example 3, and irrelevant changes were made, using Γ-(diphenylfluorenyl)-1-indenyl-1 Η-spiro [furo[3,2-g][l,4] Benzene hydrazine I嗓]-2,2'(1Ή,3Η)-dione replacement ι'_(diphenylmethyl)_6_decyloxy_5_mercaptospiro[1-benzofuranium] -2,(1Ή)-ketone, obtaining 1-mercapto-1Η-spiro[吱,[3,2-g][l,4]benzoindole_8,34 哚]-2,2,( 1Ή,3Η)-dione (73%) as colorless solid: mp. &lt;250°C (ethyl acetate); 1H NMR (300 MHz, DMSO-d6) &lt;5 10.62 (br s,1H), 7.29 -7.22 (m,1H),7·11 (d,J = 7.1 Hz,1H), 7.02-6.90 (m,2H), 6.70 (s, 1H), 6.48 (s, 1H), 4.80 (d, J = 9.2 Hz, 1H), 4.66 (d, J = 9.2 Hz, 1H), 4.58 (s, 2H)' 3.07 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6) (5 178.1, 163.3, 156.7, 146.2, 141.9, 132.3, 128.9, 124.0, 123.9, 122.9, 122.3, 109.9, 99.1, 80.3, 67.1, 57.7, 28.0; MS (ES+) m/z 322.9 (M + 1). Example 3.23 4-decyl -4,7-dihydrospiro[benzofuro[5,6-b][l,4]indole-8,3'-dihydroanthracene-2',3(2H)-dione Synthetic ch3

7-[1-(Diphenylindenyl)-2-keto-2,3-dihydro-1H-indol-3-yl]-6-hydroxy- 4-indenyl-2H-1,4- Benzoindole-3(4H)-one (3.4 g, 7.1 mmol) in anhydrous tetrahydro 143924-sp-20091127-2 •410· 201020257 bite in a solution of south (30 ml) for dry wind deoxidation 1 hour. Carbonate (8.1 g, 25 mmol) and gas-based iododecane (1.5 mL, 21 mmol) were added and the heterogeneous reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was filtered through a pad of Celite pad and the pad was washed with ethyl acetate (5 mL). The filtrate was concentrated in vacuo and the crude material was purified eluting EtOAc EtOAc EtOAc EtOAc Base-2,3-dihydro-1H-indol-3-yl]-5-yl-3-ylidene-l,3-benzoxazole-2(3H)-one. Containing trifluoroacetic acid "μ(diphenylmethyl)_2_ fluorenone 2,3_dihydro-1H-threazol-3-yl]-5-pyridyl-3-methyl-1,3- in (10 ml) To a solution of the benzoxazole-2(3H)-one (1.0 g, 20 mmol) was added triethyl decane (1.6 mL, 10 mmol), and the reaction mixture was heated under reflux for 16 hours. The reaction mixture was concentrated in vacuo and the crude was purified eluting eluting eluting elut elut Snail [benzofuro[5,6-b][l,4]噚耕-8,3,-dihydro&lt; 哚]-2',3(2H)-dione (0.52 g '78%) 'as an off-white solid: melting point &gt;25〇〇c; iH NMR (300 MHz, DMSO-d6) (5 10.63 (s, 1H), 7.28-7.23 (m, 1H), 7.10 (d, J = 7.1 Hz, 1H), Camp 6.99-6.90 (m, 2H), 6.87 (s, 1H), 6.36 (s, 1H), 4.81 (d, J = 9.3 Hz, 1H), 4.70 (d, J = 9.3 Hz, 1H) , δ 178.0, 164.4, 156.0, 141.7, 139.2 1 〇 9.8, 97.8, 79.7, 67.0, 57.6, 28.1 ; MS (ES-) m/z 321.2 (Ml). Example 3.24 2,3,6'7_tetrahydrospich-[3,2-g Synthesis of terpene-5,3'-W哚]々'(ΓΗ)-hole 143924-sp-20091127-2 •411 - 201020257

Press "," as described in Example 3, and perform irrelevant changes using Γ-(diphenylfluorenyl)_2,3,6,7-tetrahydrospiro[吱,[3,2 g] Terpene·5,3,_吲哚]-2'(1Ή)-ketone replacement (diphenylfluorenyl)_6_methoxy_5-mercaptospirobenzofuran-3,3'-吲哚]-2 '(1'H)-ketone, 2,3 6 7_tetrahydrospiro[吱,[3,2_g]nonene-5,3. 嗓]-2'(1'H)-one (63) %), as a colorless solid: iH NMR (3 〇〇 MHz, CDC13) δ 9.33 (s, 1H), 7.32-6.90 (m, 4H), 6.38 (s, 1H), 6.34 (s, 1H), 4.80- 4.71 (m, 1H), 4.46 (t, J = 8.6 Hz, 2H), 4.37-4.29 (m, 1H), 2.93 (t, J = 8.5 Hz, 2H), 2.30-2.13 (m, 2H) ; 13C NMR (75 MHz, CDC13) &lt;5 182.7, 160.6, 155.5, 140.5, 135.9, 128.3, 124.0, 123.8, 123.0, 120.3, 112.1, 110.1, 98.5, 71.9, 62.0, 48.5, 32.4, 28.9; MS (ES+) m/z 293.8 (M + 1) Example 3.25 (3S)-6-decyloxy-5-mercaptospiro[1-benzofuran-3,3,-indole]-2,(1Ή)-one Synthesis

6-Methoxy-5-methylspiro[1-benzofuran-3,3·-(4)哚]-2, (1Ή)-_ (2.16 g per operation, 0.10 g) is in a semi-preparative pair On the palmate column, it was resolved using 10% acetonitrile in a third-butyl methyl ether. (3S)-6-Methoxy-5-mercaptospiro[1-benzopyrene]-2'(1Ή)-one was isolated as a crystalline colorless solid (0.96 g, 89% recovery) :ee &gt; 99% (analyzed chiralpak ΙΑ, 1:1 acetonitrile / tert-butyl decyl ether); melting point &gt; 250 ° C; iHNMRGOOMHz 'DMSO-^) δ 10.57 (s, 1H), 7.23 (ddd , J = 7.6, 7.6, 1.3 Hz, 1H), 7.07 (d, J = 6.8 Hz, 1H), 143924-sp-20091127-2 -412- (8) 201020257 6.99-6.89 (m, 1H), 6.61 (s, 1H), 6.45 (s, 1H), 4.81-4.74 (m, 1H), 4.64 (d, J = 9.2 Hz, 1H), 3.77 (s, 1H), 1.95 (s, 1H) ; 13C NMR (75 MHz , DMSO-d6) &lt;5 179.2, 160.4, 158.9, 142.2, 133.4, 129.1, 124.4, 124.2, 122.7, 120.3, 118.4, 110.2, 94.3, 80.1, 58.0, 56.0, 16.0; MS (ES+) m/z 282.0 (M + 1). Example 3.26 Synthesis of (3R)-6-methoxy-5-methylspiro[1-benzofuran-3,3'-&lt;哚]-2,(1Ή)-one

6-decyloxy-5-mercaptospiro[1-benzofuran-3,3·-吲哚]-2'(1Ή)-one (2.16 g per operation, 〇·1 gram) is in the middle Preparative versus palmitic ία column was resolved using 10% acetonitrile in a third-butyl decyl ether. (R)-6-Methoxy-5-methyl-2indole-spiro[benzofuran-3 indoline]-2'-one is isolated as a crystalline colorless solid (0.81 g, 75% recovery) ): ee &gt; 99% (analysis of chiralpakl A, 1:1 acetonitrile / tert-butyl decyl ether); melting point &gt; 25 ° ° C; 1H NMR (300 MHz, DMSO-de) δ 10.57 (s, 1H ), 7.23 (ddd, J = 7.6, 7.6, 1.3 Hz, 1H), 7.07 (d, J = 6.8 Hz, 1H), φ 6.99-6.89 (m, 1H), 6.61 (s, 1H), 6.45 (s , 1H), 4.81-4.74 (m, 1H), 4.64 (d, J = 9.2 Hz, 1H), 3.77 (s, 1H), 1.95 (s, 1H) ; 13 C NMR (75 MHz, DMSO-d6) &lt;5 179.2, 160.4, 158.9, 142.2, 133.4, 129.1, 124.4, 124.2, 122.7, 120.3, 118.4, 110.2, 94.3, 80.1, 58.0, 56.0, 16.0; MS (ES+) m/z 282.1 (M + l) . Example 3.27 7'-Fluoro-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene-8,3W1 哚]-2'(1Ή) - Synthesis of ketones 143924-sp-20091127-2 -413- 201020257

Γ Γ 曱 ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) ) )克, U mM) Triethyl decane (〇6 mL, 丄7 mmol) was added to a solution of trifluoroacetic acid (25 mL). The reaction mixture was heated at reflux for 1 h, cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate in hexanes, and then successively developed in acetonitrile and ethyl acetate to give 7'-fluoro-2,3-dihydro snail [吱 chew and [2,3_g][1,4]benzodioxanthene-8,3|-吲哚]_2, (1,Η)-one (0.101 g, 26%), as an off-white solid :ms (es+) m/z314.2(M+l). Example 3.28 2'3,5,6-Tetrahydrospiro[benzo[i,2-b:5,4-7,]difuran-3,8,·[1,4]dioxolylene[2] Synthesis of 3-fH丨嗓]-7'(6Ή)-ketone

6,6-(Diphenylmethyl)-2,,3,,5,6-tetrahydrospiro[benzo[u_b:54,7,]difuran-3,8-[1,4]-oxoindole妇和[2,3-1]'^丨&gt;»朵]-7'(6'1'1)-_(〇.5g, 1.〇毫莫耳)

Triethylsulfonate (0.47 ml&lt;3&gt;&gt; 3.0 mmol) was added to a solution in trifluoroacetic acid (7 mL). The reaction mixture was heated at reflux for 3.5 h and concentrated in vacuo. The residue was triturated in methanol to give 2,3,5,6-tetrahydrospiro[benzo[l,2-b:5,4-b']difuran-3,8'-[ 1,4] Dioxereno[2,3〇啕哚]-7'(6Ή)-steel (0.076 g, 23%), as colorless solid: melting point &gt;(:; 1H NMR 143924-sp.20091127-2 -414· (S) 201020257 (300 MHz, DMSO-d6) δ 10.30 (s, 1H), 6.61 (s, 1H), 6.50 (s, 1H), 6.40 (s, 1H), 6.36 (s, 1H), 4.66 (ABq, J = 36.8, 9.2 Hz, 2H), 4.54-4.44 (m, 2H), 4.24-4.11 (m, 4H), 3.02-2.92 (m , 2H) ; 13C NMR (75 MHz, CDC13) δ 178.8, 160.8, 160.4, 143.3, 138.7, 135.4, 125.1, 120.9, 119.5, 118.9, 113.0, 99.0, 92.2, 79.7, 72.0, 64.2, 63.7, 57·1 , 28.3; MS (ES+) m/z 337.9 (M + 1). Example 3.29 6-decyloxy-2-keto-1,2-&lt;1&gt; 3'-p bow 丨嗓]-5-A gambling

6-decyloxy-1·-(4-methoxybenzyl)_2,·keto-oxime, 2,-dihydrospiro-benzofuran-3,3'-啕哚]-5-A Nitrile (0.50 g, L2 mmol) was added to a stirred solution of dichloromethane (5 mL) and trifluoroacetic acid (5 mL). The reaction mixture was stirred at ambient temperature for one hour&apos; and concentrated in vacuo. The residue was basified with a saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography to give 6-methoxy-2,- keto 4, 2L dihydrospiro tl benzopyrene-3'3 4 嗓]-5-indoleonitrile (0.34 g , 96%): Melting point! 85n ; 1Η NMR (300 MHz, CDC13) 5 8.46 (s, 1H), 7.30-7.25 (m, 1H), 7.11-7.03 (m, 2H), 6.97-6.94 (m, 2H), 6.56 (s, 1H ), 4.91 (ABq, 2H), 3.90 (s, 3H); MS (ES+) m/z 292.9 (M + 1) 0 Example 3.30 6-Fluoro-2'-keto-oxime, 2'-dihydrogen Snail [μBenzene sulphur _3,3, (4)] synthesis of each bet 143924-SP-20091127-2 •415· 201020257

Using a procedure as described in Example 3.29, and applying an insignificant change, using 6-fluoro-indenyl-(4-methoxybenzyl)- 2 oxy ketone ketone, 2, _ argon sulphide benzene Furan-3,3·-啕哚]-5-carbonitrile displaces 6-methoxy_Γ_(4-methoxybenzyl)_2,,yl-Γ,2,_dihydrospiro[1-benzo Furan-3,3'-吲哚]_5-indoleonitrile, 6-fluoro 2,-keto-indole, 2,-dihydrospiro[1-benzofuran-3,3,-θ丨哚]·5·carbonitrile (85%): melting point 222_224°c; ! η NMR (300 MHz, DMSO-d6) δ 10.70 (s, 1H), 7.40-7.38 (m, 1H), 7.28-7.23 (m, 2H), 7.17-7.15 (m,1H), 6.99-6.90 (m, 2H), 4.91 (ABq, 2H); MS (ES+) Spring m/z 280.9 (M + 1) ° Example 3.31 6-Methyl- Synthesis of 2,3-dihydrospiro[1,4-dioxoisene[2,3-fH哚-8,3,-W哚]_ 2',7(1Ή,6Η)-dione

6-mercapto-8-(2-nitrophenyl)-7-keto-2,3,7,8-tetrahydro-6Η-[1,4]dioxene _ sleepy and ρ- 8-Resin A (0.21 g, 0.54 mmol) and 1% w/w palladium/carbon (0.1 g) in methanol (20 mL), hydrogenated at atmospheric pressure and ambient temperature 20 hour. After passing through the furnace, the mixture was passed through, and the reduced liquid was concentrated in a vacuum. The residue was subjected to column chromatography to give 6-mercapto-2,3-dihydrospiro[1,4-dioxantho[2,3&lt;N 哚-8,3'-啕哚]- 2',7(1Ή,6Η)-dione (0.07 g, 40%): MS (ES+) m/z 323.0 ( Μ + 1). Example 3.32 -416- 143924-sp-20091127-2 (8) 201020257 4-&gt;Smelly-2,3-dihydrospiro[Nitrate benzodioxanene_8,3,_p?| 哚]- Synthesis of 2'(1Ή)-ketone

41-Bromo-1'-(diphenylmethyl)_2 3_dihydrospiro[N,3_g][14]benzodioxanthene-8,3'-吲哚]_2 , a mixture of (l,H)-ketone (5.38 g, 9.96 mmol), triethyl zebra (7.93 ml '49.8 mmol) and trifluoroacetic acid (25.9 ml, 348 mmol) at 75° Heat at C for 8 hours. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was triturated in diethyl ether, purified by column chromatography and eluted with ethyl acetate in 5% to 25% gradient of dichloromethane to give 4·-bromo-2,3-dihydrospiroindole. Fusino[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one (1.79 g, 48%) as a colorless solid : melting point &gt; 250 ° C; 1H NMR (300 MHz, DMSO-d6) δ 10.89 (s, 1H), 7.27 (dd, J = 7.9, 7.9 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H ), 6.94 (d, J = 7.6 Hz, 1H), 6.53 (s, 1H), 5.98 (s, 1H), 5.63 (ABq, 2H), 4.20-4.12 (m, 4H) ; 13 C NMR (75 MHz , DMSO-de) δ δ 176.3, 148.7, 145.1, 144.3, 139.1, 133.0, 128.7, 126.8, 120.0, 112.6, 112.2, 110.2, 105.4, 87.7, 77.6, 64.7, 64.3; MS (ES+) m/z 359.6 ( M + 1), 361.6 (M + 1). Example 3.33

4'-Fluoro-2,3-dihydrospiro[N,3-[2,3-g][l,4]benzodioxanthene-8,3'-W 哚]-2' (1Ή )-ketone synthesis

143924-SP-20091127-2 -417- 201020257 Γ-(二曱曱基 K-Fluoro-2,3-dihydrospiro[吱,[2,3-g][l,4]benzoic Oxadecene-8,3'-θ丨哚]-2'(1Ή)-one (1.18 g, 2.45 mmol) and triethyldecane (1.21 g, 9.84 mmol) in trifluoroacetic acid ( The solution in 20 ml) was heated at 65 ° C for 16 hours. After cooling to ambient temperature, the reaction mixture was concentrated in vacuo. The residue was purified from EtOAc EtOAc EtOAc. , which gives 4'-fluoro-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2 '(1Ή)-ketone (0.65 g, 84%) as colorless solid: m.p. 282-2851; 1H NMR (300 MHz, DMSO-d6) δ 10.83 (s, 1H), 7.30 (ddd, J = 8.2, 8.2 , 5.9

Hz, 1H), 6.78 (d, J = 8.0 Hz, 1H), 6.75 (d, J = 9.2 Hz, 1H), 6.47 (s, 1H), 6.27 ® (s, 1H), 4.71 (dd, J = 9.4 Hz, 2H), 4.14 (dd, J = 5.3, 3.2 Hz, 4H); 13 C NMR (75 MHz, DMSO-d6) 5 176.3, 160.9 (d, 244 Hz), 147.0, 143.3 (d, 2JC- f=96.3 Hz), 135.5, 131.9, 131.2 (d,4 Jc.F = 2.9 Hz), 128.6,128.5,123.2 (d, 2JC-f= 120 Hz), 116.4 (d, 3JC-F= 22.8 Hz) , 115.1, 108.2, 103.3, 74.3, 64.2, 63.7; MS (ES+) m/z 313.1 (M + l). Example 3.34 4-Junlin-3-yl-2,3-dihydrospiro[&gt; Furano[2,3-g][l,4]benzodioxolene _8,3,- 吲哚]·2,(1Ή)-ketone synthesis Φ

According to the procedure as described in Example 3, and the insignificant change was made, Γ-(diphenylmethyl)_4,_Jun, strain _3_yl_2,3_dihydrospiro [biting and [2] was used. , 3 magic (10) benzodioxanthene-8,3·-吲哚]-2, (1Ή)-ketone replacement (diphenylmethyl) 6-methoxy-418- 143924-sp-20091127-2

201020257 -5-methylspiro[1-benzofuran-3,3'-吲哚]-2'(1Ή)-one, 4'-porphyrin-3-yl-2,3-dihydrospiro[ Furano[2,3-g][l,4]benzodioxanthene-8,3'-throindole-2\1Ή)-嗣(99%), as pale yellow solid: mp 221- 224 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, DMSO-d6) &lt;5 10.79 (s, 1H), 8.41 (d, J = 2.2 Hz, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.75-7.68 (m, 1H), 7.58-7.53 (m, 2H), 7.40-7.33 (m, 2H), 7.04-7.00 (m, 1H), 6.93-6.88 (m, 1H) , 6.36 (s, 1H), 5.84 (s, 1H), 4.42 (d, J = 9.5 Hz, 1H), 4.25 (d, J = 9.5 Hz, 1H), 4.25-4.05 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 179.0, 155.1, 150.5, 146.9, 144.6, 142.6, © 138.3, 136.4, 135.5, 131.8, 130.1, 129.5, 129.1, 128.6, 127.3, 127.0, 124.8, 123.0, 111.2, 110.4, 98.9, 78.27, 64.7, 64.2, 58.4; MS (ES+) m/z 422.8 (M + 1). Example 3.35 4-(4-Phenoxyphenyl)-2,3-dihydrospiro (&gt; Furano[2,3_§][1,4]benzodioxanthene]_2, (ΓΗ)_ketone synthesis

曱基)-4'-(4-氡氡基笨基)_2,3_Dihydrospiro[furo[2,3_g]

143924-sp-20091127-2 -419- 201020257 -8,3·-蜊哚]-2·(1Ή)-one (74%) as an off-white solid: mp 243-246°C (diethyl ether); 1H NMR ( 300 MHz, CDC13) &lt;5 8.63-8.53 (m, 2H), 8.07 (d, J = 8.5 Hz, 1H), 7.74-7.64 (m, 2H), 7.57-7.39 (m, 2H), 7.36-7.19 (m, 3H), 7.02-6.93 (m, 2H), 6.50 (s, 1H), 5.96 (s, 1H), 5.28 (d, J = 15.8 Hz, 1H), 4.98 (d, J = 15.8 Hz, (H, 4H), 4.34 , 149.6, 147.2, 144.8, 142.7, 138.2, 137.2, 136.3, 135.7, 131.2, 130.4, 129.7, 129.2, 128.0, 126.9, 128.0, 126.9, 125.6, 122.9, 122.7, 121.8, 111.3, 109.5, 99.6, 64.6, 64.1 , 58.4,

46.3 ; MS (ES+) m/z 463.9 (M + 1) 〇Q Example 3.36 2·-keto-oxime, 2·-dihydrospiro [μbenzofuran_3,3W丨哚]_6_carbonitrile synthesis

Γ-(Diphenylmercapto keto-oxime, 2,-dihydrospiro[丨_benzofuran_3,3,_蚓哚]6-carbonitrile (1.9 g, 4.4 mmol) in triethyl Add monofluoroacetic acid (1 ml) to the suspension in decane (5 mL). Heat the solution under reflux for 6 hours, allow to cool to the temperature of the mixture and concentrate in vacuo to obtain the ketone. Dihydrohydrospiro[1_benzofuran·3,3,-吲哚]-6-carbonitrile (0.86 g, 74%) was obtained as a colourless solid that was purified without purification. MS (ES+) _ 263 〇 M + i). Example 3.37 Synthesis of methyl 2'3 monohydrospirobin [2 3 phantom [14] benzodioxol oxime, 吲哚]-2' (1'H)-嗣143924-SP-20091127-2 (S) -420- 201020257

In 1'-(diphenylfluorenyl)-5,-methyl-2,3-dihydrospiro[N,3-g][1,4]benzodioxanthene-8,3' -吲哚]-2'(1Ή)-one (0.33 g, 〇.7 〇 mmol) in a suspension of triethyl decane (2 ml), trifluoroacetic acid (5 ml of the reaction mixture Heating at 65 ° C for 16 hours, allowing it to cool to ambient temperature, and concentrating in vacuo to give 5·_methyl 2,3-dihydrospiro[吱,[2,3_g][1,4] Benzo-oxo-oxetene-8,3'-noise]-2'(1Ή)-one (0.21 g, 60%): MS (ES+) m/z 309.9 (Μ + 1). Example 3.38 9 -Fluoro- 2,3-dihydro-spiro[吱,[2,3-g][i,4]benzodioxanthene_8 3,_ρ?| 哚]-2'(1Ή) - synthesis of 嗣

According to the procedure as described in Example 3, and with irrelevant changes, 10 uses 1 benzylidene)-9-fluoro-2,3-dihydro-spiro[吱,[2,3-g] [l,4]benzodioxanthene-8,3·-啕哚]-2,(1Ή)-ketone replacement 1·-(diphenylmethyl)_6_methoxy_5_fluorenyl snail [1-benzofuran_3,3,_啕哚]_2, (1Ή)-ketone, obtaining 9-fluoroyl 2,3 dihydro-spiro-f-f-[2,3-g][l, 4] benzodioxanthene-8,3'-noise]-2.(1Ή)-_ (72%), as colorless solid: MS (ES+) m/z 313.8 (Μ + 1). Example 3.39 7,8--Wind-6Η-Snail [biting and [2,3-g] biting -3,3'-4丨嗓]·2'(1Η)-ketone synthesis 143924-SP-20091127 -2 •421- 201020257

Follow the procedure as described in Example 3.

Example 3.40 snail N stays -3,3 - lacquered [list (1) stupid and scented] _2 ketone 5,5, bismuth oxide

According to the procedure as described in Example 3, and irrelevant changes were made, 1_(diphenylmethyl)spiro(tetra)indole_3,3,-sulfonio[2,3&lt;][1]benzofuran] was used. -2(1Η)-嗣5,5'-dioxide replacement r_(diphenylfluorenyl)_6_decyloxy_5曱yl snail • benzopyrene _3,3,5 卜 朵]-2' (1 work-ketone, obtain snail (tetra) 哚 3, 3, _p phenophene 仏 (4) (1) benzoquinone p-pyran]-2 (1H)-ketone 5,5'-dioxide (43%), grayish white Solid: 1 η NMR (300 MHz, CDC13) δ 11.01-10.88 (m, 1H), 7.86-7.67 (m, 1H), 7.40-6.96 (m, 6H), 6.40-6.30 (m, 1H), 5.07- 4.80 (m, 2H) ; 13 C NMR (75 MHz, CDC13) &lt;5 177.7, 165.5, 141.8, 135.1, 131.6, 130.1, 128.9, 128.1, 127.2, 126.5, 124.8, 124.0, 123.3, 111.3, 110.9, 80.9 , 56.7 ; MS (ES+) m/z 325.8 (M + 1). Example 3.41 Snail [吱,[3,2-6][2,1,3]benzoxadiazole-8,3'-吲哚]-2'(1'11)-keto synthesis 143924-sp-20091127-2 -422- (S) 201020257

N/o ~, as described in Example 3, and performing an insignificant change, using 1-(one methyl) snail [c-benzo benzoxazole _8,3, slanting 2, (ΓΗ> 嗣 Γ Γ '(二 甲基 methyl > 6-methoxy-5-methyl snail [L benzo sulphon 3, 3 $ eucalyptus] - 2 (1 Η) - _ 'obtained snail [ Bite and condensate [3, Ke benzo and ρ No. 2 Jun 8 '3 Qiao] 2 (1 Η)-_ (88%) ' is a colorless solid: melting point &gt; 22 〇. 〇; ljiNMR (300 MHz, DMSO- D6) &lt;5 11.69 (s, 1H), 8.96-8.89 (m, 1H), 8.47-8.40 (m, 1H), 8.16 7.70 (m, 4H), 5.93 (d, J = 9.3 Hz, 1H), 5.82 (d, J = 9.3 Hz, 1H); MS (ES+) m/z 280.0 (M + 1). Example 3.42 6-Gas-2,3-dihydrospiro[吱-benzo-dioxane Synthesis of ene-9,3,吲哚]-2'(ΓΗ)-ketone

According to the procedure as described in Example 3, and with irrelevant changes, 6-gas-based 4'-(diphenylfluorenyl)_2,3-dihydrospiro[furo[3,2f][1, 4] benzodioxanthene-9,3 丨嗓 丨嗓]-2'(1Ή)-ketone replacement Γ-(diphenylmethyl) methoxy _5_methylspiro[1-benzopyrene __3,3,_p?j哚]_2,(1Ή)__, obtain 6_Chloro-2,3_dihydrospiro[吱,[3,2-f][l,4]benzoic Oxygen lanthanum _9,3'-μ丨嗓]_2, (1 Ή)-ketone (81%), colorless solid: mp 255-257 ° C; 4 NMR (300 MHz, DMSO-d6) 5 10.66 ( s, 1H), 7.23 (dd, J = 7.5, 1.2 Hz, 1H), 7.11 (d, J = 7.5 Hz, 1H), 6.96 (dd, J = 7.5, 7.5 Hz, 1H), 6.92-6.85 (m , 2H), 4.72 (ABq, 2H), 4.14-3.92 (m, 143924-sp-20091127-2 • 423- 201020257 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.7, 151.0, 141.6, 138.9, 138.1, 131.0, 128.7, 123.5, 122.2, 117.3, 117.1, 109.6, 104.8, 81.1, 64.4, 63.6, 57.3; MS (ES+) m/z 330.1 (M + 1), 332.1 (M + 1). Example 3.43 Synthesis of 2,3-dihydrospiro[indolyl[3,2-f][l,4]benzodioxanthene-9,3L吲哚]-2,(lΉ)-ketone

'6-Alkyl-indole-(diphenylfluorenyl)-2,3-dihydrospiro[M-ando[3,2-f][l,4]benzodioxene in steel elastic container Terpene-9,3,-蜊哚]-2,(1Ή)-one (2.1 g, 4.24 mmol) was suspended in methanol (20 ml) and ethyl acetate (80 ml) with palladium/carbon (20% w/w, 0.45 g). The elastic container was pressurized with hydrogen (i2 〇 pSi), and the mixture was stirred at 60 ° C for 16 hours. The reaction mixture was cooled to ambient temperature and filtered through a pad of Celite. The filtrate was concentrated in vacuo and the residue was purified ethyl acetate to give 2,3-dihydrospiro[3,2 -f][l,4] benzodioxanthene-9,3'-吲哚]-2'(1Ή)-one (0.522 g, 42%) as colorless solid: mp 259-261 ° C ; iHNMRGOOMHz'CDsODWTa-Y.lSCm, 1H), 7.09-6.88 (m, 3H), 6.70 (d, J = 8.7 Hz, 1H), 6.39 (d, J = 8.7 Hz, 1H), 4.75 (d, J = 9.3 Hz, 1H), 4.59 (d, J = 9.0 Hz, 1H), 4.12-3.90 (m, 4H) ; 13 C NMR (75 MHz, CD3OD) δ 181.0, 157.5, 142.4, 141.3, 139.6, 133.9, 129.8, 124.5, 124.0, 119.0, 117.1, 111.0, 102.9, 82.4, 66.0, 65.2, 59.1; MS (ES+) m/z 296.2 (M + 1). Example 3.44 Synthesis of 5,6-difluorospiro[1-benzofuranium]_2'(1·Η)-one 143924-sp-20091127-2 -424- 201020257

In 1-(phenylindenyl)-5,6.difluorospiro[1_ benzofuran_3,3,吲哚]_2, (1Ή)-one (6.06 g, 13.8 mmol) in furfuryl alcohol In a solution of (1 ml), ethyl acetate (25 ml) and acetic acid (1 ml), palladium/carbon (2% W/w '2.0 g) was added to a steel-shaped container. The elastic container was pressurized with a gas (5 Torr (4), and the reaction mixture was heated at 65 ° C for 16 hours. The reaction mixture was cooled to ambient temperature and filtered through a pad of diatomaceous earth. The ester (15 ml) was washed with decyl alcohol (50 ml). The filtrate was concentrated in vacuo, and the residue was purified in methanol to give 5,6-difluorospiro[1-benzofuran_3,3 , _呻哚]_2, (1, ketone-ketone (3.63 g, 96%), as a colorless solid. melting point &gt; 2 〇〇艽; lHNMR (3 〇〇 MHz, CDC13) δ 8.00 (s, 1H), 7.32-7.27 (m, 1H), 7.15-7.05 (m, 2H), 6.97 (d, J = 7.8 Hz, 1H), 6.79 (dd, J = 10.3, 6.3 Hz, 1H), 6.62 (dd, J = 9.0, 8.0 Hz, 1H), 5.00 (d, J = 9.2 Hz, 1H), 4.73 (d, J = 9.2 Hz, 1H); 13 C NMR (75 MHz, CDCI3) δ 179.7, 156.70 (d, JC. F = 10.9 Hz), 151.3 (dd, JC.F = 248.7, 14.3 _ Hz), 145.7 (dd, JC.F = 241.6, 13.8 Hz), 140.3, 131.6, 129.4, 124.0, 123.7, 123.4 (dd, JC .F= 6.3, 3.1 Hz), 111.9 (d, JC.F= 20.4 Hz), 110.7, 100.1 (d,

Jc _ F = 22.4 Hz), 80.7, 58.4 ; MS (ES+) m/z 274.2 (M + 1). Example 3.45 Synthesis of tetrahydrospiro[吲哚-3,3'-naphtho[2,3_b]furan]-2(1H)-one

According to the procedure as described in Example 3, and the insignificant changes were made, 143924-sp-20091127-2 -425- 201020257 using phthalic acid)-5',6',7,8,-tetrahydrogen索卜朵-3,3,-荇[2,3-1)]furan]-2(1Η)-嗣substituted Γ-(diphenylmethyl)_6_methoxy·5_methyl snail Benzofuran_3 3·_ , 丨哚 丨哚]-2'(1Ή)-ketone' obtains 5,6,7,8,-tetrahydrospiro 5丨哚-3,3'-荇[2,3-7]furan]-2(1Η)-one (80%) as a colorless solid: melting point &gt;〇; 1H NMR (300 ΜΗζ, CDC13) δ 8.13 (s, 1Η), 7.33-7.19 (m, 1H), 7.16 (d, J = 7.4 Hz, 1H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.95 (d, J = 7.7 Hz, 1H), 6.68 (s, 1H), 6.49 (s, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.65 (d, J = 9.0 Hz, 1H), 2.76-2.72 (m, 2H), 2.58-2.56 (m, 2H), 1.71 (t, J = 3.2 Hz, 4H); 13 C NMR (75 MHz, CDC13) δ 180.5, 158.7, 140.4, 139.0 , 132.9, 130.2, 128.8, 126.0, 124.1, 123.6, 123.3, 110.3, 110.2, Φ 79.6, 58.6, 30.0, 29.0, 23.2, 23.0 ; MS (ES+) m/z 292.0 (M + 1). Example 3.46 Synthesis of 6-(2-decyloxyethoxy)spiro[i_benzofuran_3,3,_w哚]_2ι(1Ή) ketone

Using Γ-(diphenylmethyl)-6-(2-methoxyethoxy)spiro-benzofuran_3,3,_ according to the procedure as described in Example 3, and carrying out irrelevant changes啕哚]-2'(1Ή)-ketone replaces 1'-(diphenylmethyl)_6_methoxy_5methylspiro-_benzofuran. South-3,3'-Lingsuo-2'(1Ή)-ketone' gives 6-(2-methoxyethoxy) spiro [μbenzofuran-3,3'-4 noise]-2, (1Ή)-ketone (69%): mp 172-mt; 4 NMR (300 ΜΗζ, CDC13) (5 8.56 (s, 1H), 7.23-7.18 (m, 1H), 7.15-7.06 (m, 1H), 7.06-6.97 (m, 1H), 6.97-6.89 (m, 1H), 6.89-6.82 (m, 1H), 6.82-6.74 (m, 1H), 6.38 (s, 1H), 4.80 (ABq, 2H), </ RTI> </ RTI> <RTIgt; 201020257 Example 3.47 Synthesis of 5 (2methoxyethoxy) snail [μbenzopyrano_3,3, _10] ketone

Referring to the procedure as described in Example 3, and applying an insignificant change, use 1,-(bis #methyl&gt;5_(2.methoxyethoxy) screw benzophenanthrene m wood]- 2(1 Η)-ketone-substituted porphyrin phenyl hydrazino) methoxy _5• fluorenyl snail &amp; benzofuran 3'3 ebony]-2 (1Η), 'obtain 5_(2_曱 oxygen Ethyl ethoxy) spiro-benzofuran-3,3-^1 ^ ]-2·(1Ή)-^ (30%): 1HNMR (300MHz, CDC13) 5 8.38 (s, 1H), 7.24-7.18 (m, 1H), 7.15-7.07 (m, 1H), 7.06-6.97 (m, 1H), 6.96-6.88 (m, 1H), 6.70 6.61 (m, 1H), 6.54 (s, 1H), 6.43- 6.35 (m, 1H), 4.82 (ABq, 2H), 4.13- 3.98 (m, 2H), 3.75-3.67 (m, 2H), 3.42 (s, 1H). Example 3.48 2,3 Hydrogen snail [吱-benzodioxanthene-吲嗓]

According to the procedure as described in Example 3, and with irrelevant changes, use 1-(-phenylmethyl)_2,3_dihydrospiro[吱,[2,3f][1,4]benzo Dioxonol _7'3-indole]-2'(1'H)-ketone replacement (diphenylmethyl)_6_methoxy_5methylspiro to _benzofuran-3,3, -吲哚]_2,(1Ή),, obtain 2,3_dihydrospiro[吱,[2,3 f][1'4]benzo-indenene-7,3,-W哚] - oxime)-ketone (30%) as colorless solid: 143924-sp-20091127-2: 427-201020257 Melting point &gt;250 °C; iHNMRGOOMHiDMSOO (5 10.56 (s, lH), 7.23 (ddd, J = 7.7, 7.7, 0.5 Hz, 1H), 7.13 (d, J = 7.2 Hz, 1H), 6.99-6.90 (m, 2H), 6.21 (ABq, 2H), 4.76 (ABq, 2H), 4.26 (s, 4H); 13 C NMR (75 MHz, DMSO-d6) δ 178.3, 148.7, 144.5, 141.8, 132.3, 129.2, 128.6, 123.8, 122.5, 122.2, 114.1, 109.7, 80·2, 64·1, 63.9, 57.7; MS ( ES+) m/z 295.9 (M + 1). Example 3.49 2,3-Dihydrospiro [N-[2,3-g][l,4]benzodioxene-8,8'- Synthesis of [l,3]oxazo[5,4-e]吲哚]-7'(6Ή)-one

6'-(4-Methoxy-phenyl)_2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxene-8,8'-[ 1,3]oxazolo[5,4-eH哚]-7'(6Ή)-one (1.9 g, 4.0 mmol) in dioxane (40 ml) with trifluoroacetic acid (4 ml) In the solution, add trifluoromethanesulfonic acid (1.8 ml '20 mmol) at ambient temperature. The mixture was stirred at ambient temperature for 16 hours' and concentrated in vacuo. Water was added to the residue, and the mixture was extracted with ethyl acetate. The combined organic extracts were washed with aq. EtOAc EtOAc. The residue was purified by column chromatography and eluted with 50% ethyl acetate in hexane to give 2,3-dihydrospiro[p, s-[2,3$][1,4] benzo Dioxogene _8,841,3]pyrazolo[5,4-6]'^哚-7,(6,11)-one (0.65 g, 44%): 1H NMR (300 MHz, CDC13) (5 10.86 (s,1Η), 9.06 (s,1Η), 7.97 (d' J = 8.5 Hz, 1H), 7.14 (d, J = 8.5 Hz, 1H), 6.54 (s, 1H), 6.21 (s ,1H), 4.68 (s, 2H), 4.19-4.01 (m, 4H) ; MS (ES+) m/z 353.1 (M + 1) 〇 Example 3.50 • 428- 143924-sp-20091127-2

201020257 4',6'-Dimethoxy-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 3, and with irrelevant changes, use 1 benzoquinone) 4',6'-dimethoxy 2,3-dihydrospiro[2,3 -g][l,4] benzodioxanthene-8,3'-吲哚]-2, (rH)-one substituted Γ-(diphenylmethyl)-6-methoxy-5- Methyl spiro[1-benzofuran_3,3,_p?丨哚]_2,(1Ή)__, obtain 4,6-dimethoxy-glycolyl-2,3-dihydrospiro [2,3-g][i,4]benzodioxanthene_8,3,_啕哚]-2'(1Ή)-one (55%) : 1H NMR (300 MHz, CDC13) 6 10.42 (s,1H), 6.35 (s, 1H), 6.15 (d, J = 2.0 Hz, 1H), 6.10 (d, J = 2.0 Hz, 1H), 6.08 (s, 1H), 4.58 (ABq, 2H ), 4.17-4.03 (m, 4H), 3.72 (s, 3H), 3.58 (s, 3H); MS (ES+) m/z 356.1 (M+ 1). Example 3.51 Synthesis of snail [pyrano[2,3-g] porphyrin-8,3,- 哚 哚]-2,(1Ή)-one

According to the procedure as described in Example 3, and the insignificant change was made, [-(diphenylindenyl) snail [吱-[2,3-g]quinoxaline-8,3,-啕哚] was used. -2,(1Ή)-keto-substituted Γ-(diphenylfluorenyl)-6-methoxy-5-methylspiro[1-benzofuran-3,3,-啕哚]-(1Ή)- Ketone, obtained snail [吱. Nanhe [2,3-g] sucralin-8,3'-(9)哚]-2,(1Ή)-one (22%): melting point 206-207 ° C (ethyl acetate / hexane); NMR (300 ΜΗζ, DMSO-d6) δ 10.78 (s, 1H), 8.68-8.61 (m, 2H), 8.06 (d, J = 9.0 Hz, 1H), 7.68 143924-sp-20091127-2 -429- 201020257 (d, J - 9.0 Hz, 1H), 7.21-7.18 (m, 1H), 7.03-6.86 (m, 3H), 6.96 (ABq, 2H); MS (ES+) m/z 289.8 (M + 1). Example 4 1 -(tetrahydro-2H-piperidin-2-ylmethyl)-5,6-dihydrospiro[benzo[12_b: 5,4-7,]difuran-3,3'-oxime] -2' (1 and - ketone synthesis

5,6-dihydrospiro[benzo[1,2-7:5,4-b']difuran-3,3^5丨哚]-2Π(1Ή)-one (〇·28g' 1.0 毫a mixture of 2-(bromo-mercapto)tetrahydro-2 fluorene-* smear (0.36 g, 2.0 mmol) and cesium carbonate (1.00 g '3.0 mmol) in butanone, Stir at 80 C for 3 hours. After cooling to ambient temperature, the reaction mixture was filtered and the filtrate was evaporated under reduced pressure. The residue was subjected to column chromatography using ethyl acetate-hexane (1: 54:1) to give bis-(tetrahydro-2-indole-pyran-2-ylindenyl)-5,6-dihydro Snail [benzo[l,2-b:5,4-b']difuran-3,3,-吲哚]-2,(1Ή)-one (0.31 g, 82%) as colorless solid: 1 η NMR (300 MHz, CDC13) 5 7.38-6.94 (m, 4 Η), 6.47 (d, J = 2.9 Hz, 1H), 6.38 (s, 1H), 4.79 (ABq, 2H), 4.50 (t, J = 8.6 Hz, 2H), 4.01-3.61 (m, 4H), 3.37 (t, J = 11.1 Hz, 1H), 2.97 (t, J = 8.4 Hz, 2H), 1.97-1.27 (m, 6H) ; 13 C NMR (75 MHz, CDC13) 5 178.1 (2C), 161.7 (2C), 161.3, 161.2, 143.2, 143.1, 132.8, 132.7, 128.6 (2C), 123.5, 123.1, 123.1, 120.6, 120.5, 119.8 (2C), 119.0, 118.9, 109.7, 93.2, 93.1, 80.6, 75.7, 75.5, 72.3, 68.4 (2C), 57.7, 57.6, 45.8, 45.7, 29.6, 29.5, 29.1, 25.8, 23.0 ; MS (ES+) m/z 378.3 ( M + 1). 143924-sp-20091127-2 -430- 201020257 Example 4.1 odorylbenzyl) snail [吱 并[2 34^ 3] benzodioxolanes _7,3, old 哚]-2·(1Ή) -ketone synthesis

Snail 1&gt; Futano[2,3-f][i,3]benzodioxolene-7,3,_ 哚 哚]-2,(1Ή)-one (1.05 g ' 3.73 mmol a mixture of 4-bromo bromide (1.21 g, 4.84 mmol) and carbonated planer (1.84 g ' 5.65 mmol) in 2-butanone (25 ml)' at ambient temperature 16 hours. The mixture was diluted with ethyl acetate and filtered through celite. The filtrate was concentrated to dryness under reduced pressure. The residue was purified by flash column chromatography using hexane / ethyl acetate (9:1, to 1:1) to give 1,-(4-bromo fluorenyl) snail [吱 并 [ 2,3-f][l,3]benzodioxanthene-7,3'-indole-2'(1Ή)-one (1.42 g, 84%), as a colorless solid: m.p. 150 °C (hexane); 4 NMR (300 MHz, CDC13) (5 7.48 (d, J = 8.4 Hz, 2 Η), 7.25-7.17 (m, 4H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.12 (s, 1H), 5.89 (s, 1H), 5.88 (s, 1H), 5.02 (d, J = 15.6 Hz, 1H), 4.97 (d, J = 9.0 Hz, 1H), 4.78 (d, J = 15.6 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H); 13C NMR (75 MHz, CDC13) δ 177.8, 156.1, 149.1, 142.5, 141.9, 134.9, 132.3, 132.2, 1293, 129.1, 124.2, 123.8, 122.0, 119.4, 109.3, 103.1, 101.7, 93.8, 80.6, 58.4, 43.7; MS (ES+) m/z 452.0 (M + 1), 450.0 (M + 1). Example 4.2 1·-[(2-Alkyl-1-indolyl-1H-imidazol-5-yl)methyl]-5,6-dihydrospiro[ Synthesis of stupid [i,2-b : 5,4-b']difuran-3,anthracene-2'(1Ή)-one 143924-sp-20091127-3 •431- 201020257

Displacement of 2-(bromomethyl)tetrazol with 2-chloro-5-(carbomethyl)-indolylmethyl-1H-imidazole according to the procedure as described in Example 4 and subject to insignificant changes Hydrogen-2H- britant' obtained l'-[(2-carbyl small methyl-1H-imidazole-5-yl)methyl]_5,6-dihydrospiro[benzo[l,2-b:5 , 4-iy]difuran_3,3,_啕哚]-2,(1Ή)-one (42%), as colorless solid: 1H NMR (300 MHz, CDC13) δ 7.42-7.01 (m, 4 Η) , 6.94 (s, 1Η), cf. 6.42 (s, 1H), 6.40 (s, 1H), 5.03 (ABq, 2H), 4.77 (ABq, 2H), 4.52 (t, J = 8.6

Hz, 2H), 3.59 (s, 3H), 2.97 (t, J = 8.6 Hz, 2H); 13 C NMR (75 MHz, CDC13) δ 177.7, 162.0, 161.4, 141.7, 141.7, 132.0, 129.1, 124.2, 124.0, 123.8, 120.1, 119.8, 119.6, 118.8, 110.5, 93.3, 80.6, 72.4, 57.7, 37.8, 31.0, 29.0; MS (ES+) m/z 408.0 (M + 1), 410.0 (M + 1) 〇Example 4.3 r-[(2R),hydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[u_b: 5 4 b,]difur

143924-sp-20091127-3 •432- 201020257 and [l,2-b: 5,4-b']difuran-3,3'-吲哚]-2·(1Ή)-嗣(30%), Colorless solid: :H NMR (300 MHz, CDC13) δ 7.31-6.98 (m, 4 Η), 6.48 (s, 1H), 6.39 (s, 1H), 4.78 (ABq, 2H), 4.52 (t, J = 8.6 Hz, 2H), 4.32-4.22 (m, 1H), 3.91-3.69 (m, 4H), 2.97 (t, J = 8.4 Hz, 2H), 2.09-1.64 (m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 178.3, 161.7, 161.3, 142.8, 132.8, 128.7, 123.6, 123.2, 120.5, 119.8, 118.9, 109.6, 93.2, 80.7, 76.8, 72.4, 68.2, 57.7, 44.6, 29.1, 29.0, 25.7; MS (ES+) m/z 364.1 (M + 1). Example 4.4 ® 1L (3-mercaptobutyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲哚]-2 Synthesis of '(1Ή)-ketone

Following the procedure as described in Example 4, and carrying out an insignificant change, 2-(bromomethyl)tetrahydro-2-indole was obtained using 1-bromo-3-methylbutane to obtain ❹ 1'. -(3-methylbutyl)-5,6-dihydrospiro[benzo[1,2-7:5,4?']difuran-3,3,-啕哚]-2·(1Ή)- Ketone (58%) ' is a colorless solid: iH NMR (300 MHz, CDC13) (5 7.36-6.84 (m, 4H), 6.44 (s, 1H), 6.39 (s, 1H), 4.77 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 3.88-3.64 (m, 2H), 3.04-2.90 (m, 2H), 1.75-1.54 (m, 3H), 0.99 (d, J = 6.2 Hz, 6H) 13 C NMR (75 MHz, CDC13) δ 177.6, 161.7, 161.3, 142.4, 133.1, 128.7, 123.9, 123.1, 120.4, 119.8, 118.8, 108.5, 93.2, 80.6, 72.4, 57.7, 38.8, 36.2, 29.1, 26.1 , 22.6, 22.5; MS (ES+) m/z 350.1 (M + 1). Example 4.5 143924-sp-20091127-3 •433· 201020257 l'-[(2S)-Tetrahydropyridin-2-ylmethyl ]-5,6-Dihydrospiro[benzo[i,2-b:5,4-b']di-butan-3,3W丨哚]-2\1Ή)-Synthesis of copper

Displacement of 2-(bromomethyl)tetrahydro-(4-)bromo-acid (S)-(tetrahydrofuran-2-yl)methyl ester according to the procedure as described in Example 4 and subject to insignificant changes 2Η-'Paan, obtain l'-[(2S)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b: 5,47']difuran- 3,3'-啕哚]-2'(1Ή)-_ (56%), as colorless solid: 211 NMR (300 MHz, CDC13) δ 7.34-6.96 (m, 4H), 6.48 (d, J = 1.51 Hz, 1H), 6.38 (s, 1H), 4.77 (ABq, 2H), 4.50 (t, J = 8.6 Hz, 2H), 4.32-4.21 (m, 1H), 3.98-3.64 (m, 4H), 2.96 (t, J = 8.7 Hz, 2H), 2.09-1.63 (m, 4H); 13C NMR (75 MHz, CDC13) δ 178.3, 178.2, 161.7, 161.3, 142.9, 142.9, 142.8, 132.8, 132.7, 128.7, 128.7 , 123.7, 123.6, 123.2, 119.0, 118.9, 109.6, 109.5, 93.1, 80.7, 80.7, 76.9, 76.8, 72.4, 68.3, 68.2, 57.7, 57.7, 44.7, 44.6, 29.3, 29.1 (2C), 25.7, 25.6; MS (ES+) to Jz 364.3 (M + 1) 〇 Example 4.6 1'-(Tetrahydro-2H-bran-4-ylindenyl)_5,6-dihydrospiro[Benzene (1) VII: 5,4 b Synthesis of difuran-3J-吲哚]_2'(1Ή)-one

Follow the procedure as described in Example 4, and perform an insignificant change 143924-sp-20091127-3 -434- 201020257 Replacement of 2-(bromomethyl) with 4-(Moalylmethyl)tetrahydro-2H-pyran ))-tetrahydro-2H-pyran's obtained Γ-(tetrahydro-2H- shout-4-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b: 5,4- b'] Di-pyran-3,3'-吲嗓]-2'(1Ή)-one (69%) as colorless solid: NMR (300 MHz, CDC13) δ 7.37-6.85 (m, 4H), 6.43 (s, 1H), 6.39 (s, 1H), 4.76 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 3.97 (ABq, 2H), 3.77-3.52 (m, 2H), 3.40- 3.28 (m, 2H), 3.03-2.91 (m, 2H), 2.19-2.02 (m, 1H), 1.65-1.38 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 178.1, 161.8, 161.4, 142.8 , 132.8, 128.8, 124.1, 123.3, 120.2, 119.9, 118.8, 108.6, 93.3, 80.8, 72.4, 67.5, 57.7, 46.1, 33.9, 10 30.8, 29.1 ; MS (ES+) m/z 378_3 (Μ + 1). Example 4.7 5-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b]difuran-3,3'-吲哚]-Γ(2Ή) Synthesis of fluorenyl furan-2-carboxylate

Displacement of 2-(bromomethyl)tetrahydro-2-indole-p-ethyl ester with 5-(carbomethyl)pyran-2-carboxylic acid oxime ester according to the procedure as described in Example 4 and subject to insignificant changes Obtained 5-[(2'-keto-5,6-dihydrospiro[benzo[1,2-b:5,4-b,]difuran-3,3'-吲哚]-1 '(2Ή)-yl)methyl]nonan-2-carboxylic acid methyl ester (70%) as colorless solid: 4 NMR (300 MHz, CDC13) δ 7.28-6.23 (m, 5H), 6.49 (s, 1H), 6.39 (s, 1H), 6.37 (d, J = 3.49 Hz, 1H), 4.99 (ABq, 2H), 4.80 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 3.85 ( s, 3H), 3.05-2.92 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 177.5, 161.9, 161.3, 158.8, 153.5, 144.2, 141.4, 132.6, 128.9, 124.0, 123.8, 143924-SP- 20091127-3 -435- 201020257 120.1,120·0, 119.0,110.2,109.0, 93.2, 80.5, 72.4, 57.7, 52.0, 37.4, 29.1; MS (ES+) m/z 418.1 (M+l). Example 4.8 Γ-(1,4-Dioxin-2-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3, Synthesis of T-吲哚]-2Χ1Ή)-ketone

According to the procedure as described in Example 4, and irrelevant changes were made, 2-(bromomethyl)-1,4-dioxane was used to replace 2-(bromomethyl)tetrahydro-2-indole- '' obtained Γ-(1,4-dioxolan-2-ylindenyl)-5,6-dihydrospiro[benzo[i,2-b: 5,4-b'] diterpene- 3,3'-吲嗓]-2'(1Ή)-net (48%), as a colorless solid: ifj NMR (300 MHz, CDC13) δ Ί39-6.96 (m, 4Η), 6.45 (d, J = 8.1 Hz, 1H), 6.38 (s, 1H), 4.89 (ABq, 2H), 4.65 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 3.99-3.33 (m, 9H), 3.05-2.85 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 178.2, 178.1, 161.8, 161.8, 161.3, 161.2, 142.6, 132.7, 132.6, 128.8, 128.7, 123.8, 123.7, 123.4, 120.3, 120.2, 120.0, 119.9, 118.9, 118.8, 109.5, 109.3, 93.2, 80.6, 80.5, 73.2, 72.4, 69.3, 69.2, 66.7, 66.6, 66.4, 57.6, 41.7 (2C), 29.1 ; MS (ES+) m/z 380.1 (M+ l). Example 4.9 Γ-{[1-Methyl-3-(trifluoromethyl)-1Η-pyrazol-4-yl]fluorenyl}-5,6-dihydrospiro [stupid [l,2-b: Synthesis of 5,4-b']di-p-vector-3,3'-吲哚]-2,(1Ή)-ketone 143924-sp-20091127-3 -436- 201020257

Displacement of 2 (bromodecyl) tetra-gas with 4-(methylmethyl) 1 methyl·3 (trifluoromethyl)_1H pyrazole according to the procedure described in Example 4 and subject to insignificant changes _2H-«Trace's obtained Γ{{1_methyl_3_(trifluoromethyl)_1H_pyrazole_4_yl]methyl}-5,6-dihydrospiro[benzo: 5,4 b,]difuran_3 3,峋哚]_2, (1Ή)-ketooxime (32%), as colorless solid: NMR (300 MHz, CDC13) &lt;5 7.39 (s,1Η), 7.29-6.84 ( m, 4H), 6.42 (s, 1H), 6.38 (s, 1H), 4.89 (s, 2H), 4.79 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 3.86 (s, 3H) ), 2.97 (t, J = 8.6 Hz, 2H); 13 C NMR (75 MHz, CDC13) &lt;5 178.0,1619, 1614, 141 6, 139 9,139 4, 138 9,138 4, 132.5, 131.9 , 128.9, 124.1, 123.7, 123, 4, 120.0, 119.9, 119.8, 118.8, 115.4, 108.8, 93.3, 80.6, 72.4, 57.6, 39.7, 34.0, 29.0; MS (ES+) m/z 442.0 (M + 1) ° Example 4.10 l (tetrazo-2H- shouting) South _3-yl fluorenyl) _5,6_ dihydrospiro [benzoan-like seven: entangled,] dioxin® _3,3'-啕哚]-2 , (1Ή)-ketone synthesis

According to the procedure as described in Example 4, and irrelevant changes were made, 3-(bromomethyl)tetrahydro-2-indole-periphery was substituted for 2_(bromomethyl fine argon-2-n_piperidine to obtain r ·(四Hi °南-3-基曱基)-5,6-dihydrospiro[benzo[u_b:5'47']difur drink_3,3,_+朵]_2,(1Ή) Ketone (), a colorless solid: 4 Μ· 143924-sp-2009l 127-3 •437· 201020257 (300 MHz, CDC13) δ 7.42-6.83 (m, 4H), 6.44 (d, J = 2.3 Hz, 1H ), 6.39 (s, 1H), 4.88 (dd, J = 8.9, 1.9 Hz, 1H), 4.63 (d, J = 8.9 Hz, 1H), 4.51 (t, J = 8.6 Hz, 2H), 3.89-3.24 (m, 6H), 3.08-2.86 (m, 2H), 2.26-2.09 (m, 1H), 1.91-1.29 (m, 5H); 13 C NMR (75 MHz, CDC13) δ 178.0, 178.0, 161.8, 161.4 , 161.3, 142.5, 142.4, 132.8, 132.8, 128.8, 124.0 (2C), 123.4, 120.2, 120.1, 120.0, 119.9, 118.8 (2C), 108.6, 93.2, 93.2, 80.8, 72.4 (2C), 71.2, 71.0, 68.5, 68.4, 57.7 (2C), 42.5, 42.4, 34.8, 29.1, 27.5, 27.4, 25.1, 24.8; MS (ES+) m/z 378.1 (M + l). Example 4.11 2-[(2'-keto) -5,6-dihydrospiro[benzo[l,2-b: 5,4-b.]difuran-3,3·-啕哚]-Γ(2Ή)-yl)indolyl]-1, 3- Synthesis of oxazole-4-carboxylate

The 2-(bromomethyl)carbazole-4-carboxylic acid methyl ester was used to replace 2-(bromomethyl)tetrahydro-2-indole_pyran, according to the procedure described in Example 4, and the insignificant change was performed. 2-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b1]difuran-3,3,-吲嗓]-Γ(2Ή) is obtained. -yl)methyl]-1,3-, oxazole-4-carboxylic acid decyl ester (61%) as a colorless solid: 1H NMR (300 MHz, CDC13) δ 8.17 (s, 1 Η), 7.27-6.91 ( m,4Η), 6.53 (s, 1Η), 6.38 (s, 1H), 5.12 (ABq, 2H), 4.81 (ABq, 2H), 4.51 (t, J = 8.7 Hz, 2H), 3.89 (s, 3H) ), 3.04-2,91 (m, 2H); 13C NMR (75 MHz, CDC13) 5 177.6, 161.9, 161.2 (2C), 159.2, 145.0, 141.0, 133.6, 132.5, 129.0, 124.1, 120.1, 119.9, 199.1 , 108.8, 93.2, 80.5, 72.4, 57.7, 52.3, 37.2, 29.0. 143924-sp-20091127-3 -438- 201020257 Example 4.12 (2-|L-decyl)_5,6·dihydrospiro[benzo[[7]: 2:3, p1| 哚]-2' (1Ή)-ketone synthesis

According to the procedure as described in Example 4, and irrelevant changes were made, 2- 置换 溴 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- 2- Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ Γ (2-fluoro-yl)-5,6-dihydrospiro[benzox,2_b: 5,4_b,]difuran_3,3,_啕嗓]-2'(1Ή)-鲷(81%) , is a colorless solid: Η Η 尺 (3〇〇2, CDCl3) 7.41-6.81 (m, 8H), 6.47 (s, 1H), 6.41 (s, 1H), 5.02 (ABq, 2H), 4.83 ( ABq, 2H), 4.52 (t, J = 8.7 Hz, 2H), 3.08-2.89 (m, 2H); 13C NMR (75 MHz, CDC13) δ 178.0, 162.3, 161.9, 161.4, 159.0, 141.9, 132.7, 129.7 , 129.7 (2C), 129.6, 128.9, 124.7, 124.6, 123.9, 123.5, 122.9, 122.7, 120.2, 120.0, 119.0, 115.8, 115.5, 109.1, 109.0, 933, 80.7, 72.4, 57.38, 37.6, 37.5, 29.1; MS φ (ES+) m/z 387.9 (M + 1) 〇 Example 4.13 Γ-(4-fluorobenzyl)-5,6-dihydrospiro [stupid [l,2-b: 5,4-b' Synthesis of difuranium]-2\1Ή)-one

143924-sp-20091127-3 439- 201020257 Following the procedure as described in Example 4, and carrying out irrelevant changes, the replacement of 2-(bromomethyl) four with 4-fluorophenyl Hydrogen-2H-pyran to obtain Γ-(4-fluoroindolyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-啕哚]-2'(1Ή)-one (80%) as a colorless solid: 1H NMR (300 MHz, CDCl3) 5 7.41-6.94 (m, 7H), 6.79 (d, J = 7.8 Hz, 1H), 6.44 (s, 1H), 6.41 (s, 1H), 4.91 (ABq, 2H), 4.83 (Abq, 2H), 4.53 (t, J = 8.7 Hz, 2H), 3.08-2.89 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 178.0, 164.0, 161.9, 161.4, 160.7, 141.9, 132.8, 131.7, 131.6, 129.3, 129.2, 128.7, 124.0, 123.5, 120.2, 120.0, 118.8, 116.0, 115.7, 109.1, 93.3 , 80.6, 72.4, 57.7, 43.5, 29.1; MS (ES+) m/z 387.9 (M + 1). Example 4.14 Indole-indolyl-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-anthracene-2,(1Ή)-one Synthesis

According to the procedure as described in Example 4, and irrelevant changes were made, 2-(bromomethyl)tetrahydro-2-indole-[ranine was replaced with benzyl bromide to obtain Γ-benzyl-5,6-di. Hydrogen snail [benzo[l,2-b:5,4-b.]difuran-3,3,-啕哚]-2,(1Ή)-_ (89%) as a colorless solid: 1H NMR ( 300 MHz, CDC13) δ 7.43-6.96 (m, 8 Η), 6.80 (d, J = 7.8 Hz, 1H), 6.48 (s, 1H), 6.42 (s, 1H), 4.96 (ABq, 2H), 4.84 ( ABq, 2H), 4.53 (t, J = 8.7 Hz, 2H), 3.05-2.92 (m, 2H); 13C NMR (75 MHz, CDC13) δ 178.0, 161.8, 161.4, 142.2, 135.8, 132.8, 128.9, 128.7 , 127.8, 127.4, 123.9, 143924-sp-20091127-3 201020257 123.4, 120.3, 120.0, 118.9, 109.3, 93.3, 80.7, 72.4, 57.8, 44.2, 29.1 ; MS (ES+) m/z 369.9 (Μ + 1) . Example 4.15 1|-(Biphenyl-4-ylindenyl)-5,6-dihydrospiro[benzo[1,2-1]:5,4-7,]difuran-3,3'-&lt;哚]-2|(1Ή)-嗣 Synthesis

According to the procedure as described in Example 4, and irrelevant changes were made, 2-(chloromethyl)biphenyl was substituted for 2-(bromomethyl)tetrahydro-2-indole-pyran to obtain hydrazine-(biphenyl). 4-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-7]difuran-3,3·-吲哚]-2'(1Ή)-one ( 39%), as a colorless solid: iH NMR (300 MHz, CDC13), 7.67-6.81 (m, 13H), 6.50 (s, 1H), 6.44 (s, 1H), 5.00 (ABq, 2H), 4.86 (ABq , 2H), 4.54 (t, J = 8.7 Hz, 2H), 3.09-2.90 (m, 2H); 13C NMR (75 MHz, Θ CDC13) δ 178.0, 161.9, 161.4, 142.1, 140.8, 140.5, 134.8, 132.8 , 128.8, 127.9, 127.6, 127.5, 127.1, 123.9, 123.5, 120.3, 120.0, 118.9, 109.3, 93.3, 80.7, 72.4, 57.8, 43·9,29·1 ; MS (ES+) m/z 445.9 (M + 1). Example 4.16 1*-(Tetrahydrofuranylmethyl)-5,6-dihydrospiro[benzo[l,2-b··5,4-7,]difuran-3,3Ί嗓]-2' (1Ή )-keto synthesis 143924-sp-20091127-3 -441 - 201020257

Following the procedure as described in Example 4, and carrying out an insignificant change, 2-(bromomethyl)tetrahydro-2H-pyran was replaced with 3-(indiylthio)tetrahydrofuran to give 1'-(tetrahydrofuran-3). -5,6-dihydrospiro[benzo[12_b:5 4_b,]difur--3,3'-+)] (83%) ' is a colorless solid: iH nmr (300 MHz, CDC13) δ 7.39-6.89 (m, 4H), 6.42 (s, 1H), 6.39 (s, 1H), 4.77 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 4.01-3.54 (m , 6H), 3.04-2.91 (m, 2H), 2.89-2.75 (m, 1H), 2.10-1.95 (m, 1H), 1.82-1.68 (m, 1H) ; 13 C NMR (75 MHz, CDC13) δ 178.1, 178.0, 161.8, 161.3, 142.4 (2C), 132.8 (2C), 128.8, 124.0 (2C), 123.4, 120.2, 120.1, 119.9 (2C), 118.7, 118.6, 108.4, 108.3, 93.2 (2C), 80.6 , 72.3, 71.1, 70.9, 67.6, 67.5, 57.6, 42.8, 42.7, 38.0 (2C), 29.8 (2C), 29.1; MS (ES+) m/z 364.0 (M + 1). Example 4.17

143924-sp-20091127-3 -442· 201020257 5,4-b·]difuran-3X 哚]-2·(1Ή)-one (58%) as colorless solid: 4 NMR (300 MHz, CDC13) δ 7.36-6.88 (m, 4Η), 6.44 (s, 1H), 6.40 (s, 1H), 6.33 (s, 1H), 5.05 (ABq, 2H), 4.80 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H), 3.07-2.89 (m, 2H); 13C NMR (75 MHz, CDC13) (5 178.1, 161.7, 161.2, 142.8, 132.6, 128.6, 123.6, 123.2, 120.3, 119.8, 118.8, 109.4, 93.1 , 80.6, 76.9, 72.3, 68.2, 57.6.44.6, 29.2, 29.0, 25.5; MS (ES+) m/z 438·7 (M + 1), 440 (M + 1). Example 4.18 Γ-[(5- Bromofuran-2-yl)indolyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran®-3,3'蚓哚]-2' ( 1Ή)-ketone synthesis

Displacement of 2-(bromomethyl)tetrahydro-2-indole-peryl bromide with 2-bromo-5-(indiyl sulfhydryl) acetonate according to the procedure as described in Example 4, and subject to insignificant changes. Obtained Γ-[(5-bromofuran-2-yl)indolyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3' -W 哚]-2'(ΓΗ)-ketone (94%) as a colorless solid: iH NMR (300 MHz, CDCI3) δ 7.33-6.96 (m, 4H), 6.46 (s, 1H), 6.40 (s, 1H), 6.28 (dd, J = 23.3, 3.3 Hz, 2H), 4.89 (ABq, 2H), 4.80 (ABq, 2H), 4.52 (t, J = 8.6 Hz, 2H), 3.07-2.88 (m, 2H) 13C NMR (75 MHz, CDC13) &lt;5 177.4,161.8,161.2, 151.0, 141.5, 132.7, 128.7, 123.8, 123.6, 121.6, 120.1, 119.9, 118.9, 112.3, 111.4.109.0, 93.2, 80.4, 72.4 , 57.6, 37.0, 29.0; MS (ES+) m/z: 437.7 (M + 1), 439.7 (M + 1). Example 4.19 143924-sp-20091127-3 -443- 201020257 Γ-(tetrahydrofuran-2-ylmethyl)_5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran -3,3.卜来]-2'(1Ή)-_ Synthesis

Following the procedure as described in Example 4, and carrying out irrelevant changes, 2-(bromomethyl)tetrahydrofuran was substituted for 2-(bromomethyl)tetrahydro-2-indole-pyran to give 1'-(tetrahydrofuran- 2-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuryl-3,3'-吲哚]-2'(1Ή)- Brewing I (64%), colorless solid: 1 η NMR (3〇〇MHz, CDC13) δ 7.37-6.95 (m, 4H), 6.48 (d, J = 1.2 Hz, 1H), 6.38 (s, 1H) , 4.78 (ABq, 2H), 4.50 (t, J = 8.7 Hz, 2H), 4.31-4.21 (m, 1H), 3.98-3.65 (m, 4H), 2.96 (t, J = 8.7 Hz, 2H), 2.09-1.64 (m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 178.3, 178.2, 161.7, 161.2, 142.8 (2C), 132.7, 132.6, 128.7, 123.6, 123.2, 120.4 (2C), 119.8, 118.9 (2C), 109.5, 109.4, 93.1, 80.7, 80.6, 76.9, 76.8, 72.3, 68.2, 68.1, 57.6 (2C), 44.6, 44.5, 29.2, 29.0, 25.6, 25.5; MS (ES+) m/z 363.8 ( M + 1) 〇 Example 4.20 1'-(glycidyl-2-ylmethyl)_5,6-dihydrospiro[benzo[[7:5,4_bl]difuran-3,3-Μ丨嗓Synthesis of ]·2'(ι'η)-_

According to the procedure as described in Example 4, and the insignificant change was carried out 143924- sp-20091127-3 (S) -444 - 201020257 Replacement of 2-propenylbenzenesulfonate propylene oxide-2-yl decyl ester 2- (Bromomethyl)tetrahydro-2H-pyran' obtained Γ-(propylene oxide-2-ylmethyl)_5,6-dihydrospiro[benzo[i,2-b: 5,4-b '] Diterpene-3,3'-啕嗓]-2'(1Ή)-one (28%) as a colorless solid: ifj NMR (300 MHz, CDC13) δ 7.34-6.95 (m, 4H), 6.41 (d, J = 9.2 Hz, 1H), 6.38 (s, 1H), 5.04-4.90 (m, 1H), 4.80-4.62 (m, 2H), 4.52-4.30 (m, 4H), 4.08-3.76 (m , 2H), 2.91 (t, J = 8.6 Hz, 2H), 2.70-2.56 (m, 1H), 2.44-2.33 (m, 1H) ; 13C NMR (75 MHz, CDC13) 5 178.0, 177.8, 161.5, 161.0 (2C), 143.5, 143.4, 132.5, 132.4, 129.0, 128.9, 123.8, 123.7, 123.3, 121.0 (2C), 120.3, 119.3, ® 119.2, 110.3, 110.2, 92.9 (2C), 80.3 (2C), 79.8, 79.6, 72.5, 68.0, 57.3 (2C), 45.8 (2C), 28.8, 28.7, 25.0, 24.7; MS (ES+) ra/z 349.8 (M + 1). Example 4.21 Ethyl-1H-imidazol-5-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-oxime哚]-2'(1Ή)-ketone synthesis

Following the procedure as described in Example 4, and performing an insignificant change, replacing 2-(bromohydrazino) with 5-(carbomethyl)-1-ethyl-1Η-imidazole-3-imidinium chloride四-[(ΐ-ethyl_1Η-imidazol-5-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b: 5, 4-b']difuran-3,3,-anthracene-2, (1Ή)-_ (57%), as colorless solid: 1H NMR (300 MHz, CDC13) &lt;5 7.34-6.95 (m, 4Η), 6.41 (d, J = 9.2 Hz, 1H), 6.38 (s, 1H), 5.04-4.90 (m, 1H), 4.80-4.62 (m, 2H), 4.52-4.30 (m, 4H), 4.08 -3.76 (m, 2H), 2.91 (t, J = 8.6 Hz, 2H), 2.70-2.56 (m, 1H), 2.44-2.33 143924-sp-20091127-3 -445- 201020257 (m, 1H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 177.8, 161.5, 161.0 (2C), 143.5, 143.4, 132.5, 132.4, 129.0, 128.9, 123.8, 123.7, 123.3, 121.0 (2C), 120.3, 119.3, 119.2, 1103, 110.2, 92.9 (2C), 80.3 (2C), 79.8, 79.6, 72.5, 68.0, 57.3 (2C), 45.8 (2C), 28.8, 28.7, 25.0, 24.7; MS (ES+) m/z 349.8. Example 4.22 3-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7']difuran-3,3|-吲哚]-1' (2 ·!!)-Based on the synthesis of benzonitrile

5,6-Dihydrospiro[benzo[l,2-b ··5,4-b']difuran-3,3·-吲哚]-2,(1Ή)-one (0.97 g, 3.46 To a solution of 2-butanone (25 ml), a carbonic acid planer (3.39 g, 10.39 mmol) and a-bromo-m-toluenecarbonitrile (0.85 g, 4.33 mmol) were added. The mixture was heated to reflux over 2 hours, cooled to ambient temperature and filtered. The solid was washed with ethyl acetate. The filtrate was concentrated in vacuo and the residue was purified eluting elut elut elut elut elut 2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran-3,3Wbdu]-Γ(2Ή)-yl)indenyl]benzene Benzonitrile (1.26 g, 92%) as colorless solid: m.p.: 187-193 ° C; iHNMRGOO MHz, CDC 13) 5 7.61-7.58 (m, 3H), 7.47-7.44 (m, 1H), 7.25-7.19 (m , 2H), 7.07-7.03 (m, 1H), 6.73-6.71 (m, 1H), 6.43-6.41 (m, 2H), 5.11-4.70 (m, 4H), 4.53 (d, J = 9.0 Hz, 2H ), 3.09-2.91 (m, 2H); 13 C NMR (75 MHz, CDC13) 5 178.1, 162.0, 161.4, 141.5, 137.5, 132.6, 131.9, 131.6, 130.7, 129.9, 128.9, 124.3, 123.9, 120.2, 119.9 , 118.7, 118.4, 113.1, 108.8, 93.4, 80.5, 72.5, 57.7, 143924-sp-20091127-3 -446- 201020257 43.4, 29.0 ; MS (ES+) m/z 394.8 (Μ + 1). Example 4.23 4-((2'-keto-5,6-dihydro-2Η-spiro[benzopyrano[6,5_b]p-fol-3,3·-dihydroindole]-Γ- Synthesis of benzonitrile

According to the procedure as described in Example 4.22, and irrelevant changes were made, 4-(bromomethyl)benzonitrile was used to replace (6) odor-m-toluene.carbonitrile to obtain 4_2, keto-5. 6-Dihydro-2Η-spiro[benzofuro[6,5-b]furan_3,3,-diazepine]-Γ-yl)mercapto)benzonitrile (88%) as colorless solid: mp 69-71 〇c ; 1 η Nmr (300 MHz' CDC13) 6 7.73-7.56 (m, 2H), 7.50-7.40 (m, 2H), 7.22-7.15 (m, 2H), 7.10-7.00 (m, 1H), 6.75 -6.66 (m, 1H), 6.47-6.38 (m, 2H), 4.99 (ABq, 2H), 4.83 (ABq, 2H), 4.54 (t, J = 8.6 Hz, 2H), 3.06-2.92 (m, 2H) ); MS (ES+) m/z 395.0 (M + 1). Example 4.24 Heart (6)-keto-known-dihydrospiro-reducing and similar to seven: ^ seven-renofuran (5), ·... 哚]-Γ(2Ή)-yl)methyl]biphenyl-2-indene nitrile

Following the procedure as described in Example 4, and performing an insignificant change 143924-sp-20091127-3 -447- 201020257 Replacement of 2-(bromohydrazino) with 4-bromodecyl-2-cyanobiphenyl Tetrahydro-2H-pyran to obtain 4,-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3 '-β 哚]-Γ(2Ή)-yl)methyl]biphenyl-2-indene nitrile (81%) as colorless solid: mp 192-194 〇 C; 1H NMR (300 MHz, CDC13) δ 7.74 (d, J = 7.7 Hz, 1H), 7.63 (ddd, J = 7.6, 7.6, 1.1 Hz, 1H), 7.58-7.39 (m, 6H), 7.27-7.15 (m, 2H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.42 (s, 1H), 5.12 (d, J = 15.7 Hz, 1H), 5.00 (d , J = 9.0 Hz, 1H), 4.91 (d, J = 15.7 Hz, 1H), 4.72 (d, J = 9.0 Hz, 1H), 4.53 (t, J = 8.6 Hz, 2H), 3.09-2.90 (m , 2H); 13 C NMR (75 MHz, CDC13) &lt;5 178.0, 161.9, 161.4, 144.8, 142.1, 137.7, 133.9, 〇133.0, 132.8, 130.1, 129.3, 128.9, 127.8, 124.0, 123.6, 120.2, 120.0 , 119.0, 118.7, 111.1, 109.3, 93.3, 80.7, 72.4, 57.8, 43.9, 29.1; MS (ES+) m/z 471.0 (M+ 1). Example 4.25 r-{(2S)-2-[(Benzyloxy)methoxy]propyl b 5,6-dihydrospiro[benzo[u_b:5 4-7,]difuran-3,3'-吲哚]-2'(1Ή)-ketone synthesis

Displacement of 2 (bromomethyl)tetrahydro-2-indole-periphidine with 4-nonylbenzenesulfonic acid (5)_2_(;oxydecyloxy)propyl ester according to the procedure as described in Example 4 and subject to insignificant changes Ran, obtain r_{(2s)_2_[(yloxy)methoxy]propyl} 5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]difuran-3, 3,-啕哚]-2,(1Ή)-one (61%), as colorless solid: m.p. 49-52t:; 4 NMR (300 MHz, CDC13) ( diastereomers) 5 Z36-7.22 ( m,4H), 7.20-6.99 (m,5H),6.44 (d,J = 12.8 Hz,1H) 143924-sp-20091127-3 •448- 201020257 6.39 (s, 1H), 4.89-4.61 (m, 4H ), 4.56-4.33 (m, 4H), 4.28-4.13 (m, 1H), 3.96-3.70 (m, 2H), 3.03-2.70 (m&gt; 2H), 1.29 (dd, J = 6.1, 3.1 Hz, 3H 13C NMR (75 MHz, CDCI3) (diastereomer) 3 178丄161 6 (2), 143 〇(2), 137.6 (2), 132.7 (2), 128.7 (2), 128.5, 127.8 (2), 127.6 (2), 123.8 (2), 123.2 (2), 120.3 (2), 119.9 (2), 119.0, 109.6 (2), 93.2 (2), 93·0 (2), 80.7 (2 ), 72.4 (2), 71.5 (2), 69.5 (2), 57.6 (2), 46.2 (2), 29.0 (2), 18.3 (2); MS (ES+) m/z 479.9 (M + 23). Example 4.26 l'-(2'3-Dihydro-1,4-benzodioxanthene-6-ylmethyl)_5,6-dihydrospiro[benzo[l,2-b: 5, Synthesis of 4-b']difuran_3,3,-吲哚]-2,(1Ή)-one

6-(Xiylmethyl)-2,3-dihydrobenzo[b][i,4]dioxene terpene was substituted 2 according to the procedure as described in Example 4, and the insignificant change was performed. -(bromomethylidenemethyl)tetraar-2H-pyran to obtain i'-(2,3-dihydro-1,4-benzodioxanthene-6-ylindenyl)-5,6 - Dihydrospiro [benzo[1,2-7:5,4-7,]difuran-3,3,-anthracene-2, (1,11)-one (86%) as a colorless solid: melting point 173_175»c (diethyl ether/hexane); ihnmr (300 MHz, CDCI3) δ 7.21 (dd, J = 7.8, 7.8 Hz, 1H), 7.16 (d, J = 6.9 Hz, 1H), 7.02 (dd, J = 7.5, 7.02 Hz, 1H), 6.86-6.80 (m, 4H), 6.49 (s, 1H), 6.43 (s, 1H), 4.98 (d, J = 9.0 Hz, 1H), 4.94 (d, J = 15.2 Hz, 1H), 4.75 (d, J = 15.2 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.54 (t, J = 8.6 Hz, 2H), 4.24 (s, 4H), 3.09- 2.92 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 111.9, 161.9, 161.4, 143.8, 143.3, 142.3, 132.9, 129.1, 128.8, 123.9, 123.4, 120.6, 120.4, 120.0, 119.1, 117.7, 143924- Sp-20091127-3 -449- 201020257 116.5, 109.5, 93.3, 80.8, 72.5, 64.45, 64.41, 57.8, 43.7, 29.2; MS (ES+) m/z 428.0 (M + 1). Example 4.27 Γ-(2,1,3-benzoxazol-5-ylindenyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran Synthesis of -3,3'-吲哚]-2'(1Ή)-ketone

Following the procedure as described in Example 4, and carrying out an insignificant change, using 5-(indiylthio)-2,1,3-1,3-dioxadiazole to displace 2-(indiylmethyl)tetrahydro- 2Η-pyran to obtain Γ-(2,1,3-benzoxazol-5-ylindenyl)-5,6-dihydrospiro[benzo[l,2-b: 5,4-b ']Difuran-3,3'-indole]-2,(1Ή)-one (74%) as colorless solid: mp 169-171 ° C; 1H NMR (300 MHz, DMSO-d6) 6 8.06 ( d, J = 8.6 Ηζ, 1H), 8.01 (s, 1H), 7.49 (dd, J = 9.3, 1.3 Hz, 1H), 7.28-7.14 (m, 2H), 7.12-6.98 (m, 2H), 6.46 (s, 1H), 6.40 (s, 1H), 5.14-4.97 (m, 2H), 4.89 (d, J = 9.5 Hz, 1H), 4.74 (d, J = 9.5 Hz, 1H), 4.57-4.35 ( m, 2H), 3.04-2.82 (m, 2H); 13C NMR (75 MHz, DMSO-d6) &lt;5 177.9, 161.7, 161.2, 149.3, 148.9, 142.4, 141.8, 133.2, 132.7, 129.2, 124.2, 123.8 , 120.9, 120.4, 119.4, 117.3, 113.5, 109.8, 93.0, 80.4, 72.6, 65.4, 57.4, 43.7, 28.8; MS (ES+) m/z 411.9 (M + 1). Example 4.28 Γ-(2,1,3-benzothiadiazol-5-ylmethyl)-5,6-dioxaspiro[benzo[1,2-b : 5,4-b']di 143924 -sp-20091127^3 -450- 201020257

Displacement of 2-(bromomethyl)tetrahydro-2H_ with 5-(bromomethyl)-2,1,3-benzopyrazole according to the procedure as described in Example 4, and with irrelevant changes Piperine, obtaining Γ-(2,1,3-benzoxadiazole fluorenyl)_5,6-dihydrospiro[benzoxan[l,2-b:5,4?']difuran- 3,3'-called 哚]-2,(1Ή)-one (74%), as colorless solid: mp 162-164 C; 1H NMR (300 MHz, DMSO-d6) 5 8.12-8.04 (m, 2 Η) , 7.63 (dd, J = 9.3, 1.5 Hz, 1H), 7.27-7.14 (m, 2H), 7.09 (d, J = 7.7 Hz, 1H), 7.00 (dd, J = 7.5, 7.5 Hz, 1H), 6.42 (s, 1H), 6.40 (s, 1H), 5.23-5.05 (m, 2H), 4.88 (d, J = 9.5 Hz, 1H), 4.73 (d, J = 9.5 Hz, 1H), 4.55-4.38 (m, 2H), 3.04-2.82 (m, 2H); 13C NMR (75 MHz, DMSO-d6) &lt;5 177.8, 161.7, 161.2, 154.7, 154.2, 142.5, 139.0, 132.6, 130.2, 129.2, 124.2, 123.7, 122.3, 120.9, 120.4, 119.6, 119.3, 109.9, 93.0, 80.3, 72.6, 57.5, 43.5, 28.8; MS (ES+) m/z ❹ 427.9 (M + 1). Example 4.29 Γ-[(4-Benzylmorpholine-2-yl)methyl]_5,6-dihydrospiro [benzophenyrimidine: 5,4-7,]difuran-3,3·-啕哚] -2'(1Ή)-_ synthesis

Follow the procedure as described in Example 4 and perform irrelevant changes ' 143924-sp.20091127-3 •451- 201020257 Replacement of 2-(bromomethyl) with 4-mercapto-2-(ylmethyl)morphine Base) tetrahydro-2H_^ 0 south's paid 1 -[(4 今基福福林-2-yl)methyl]-5,6-dihydrospiro[benzo[i,2_b : 5,4 -b']difuran-3,3'-indole]-2'(1'H)-one (10%) as a colorless solid: mp. 65_7 〇C*H NMR (300 MHz, CDC13) δ 7.35- 7.00 (m, 9Η), 6.49-6.39 (m, 2H), 4.92-4.84 (m, 1H), 4.69-4.49 (m, 3H), 3.93-3.42 (m, 7H)S 3.02-2.54 (m, 4H ), 2.22-2.00 (m, 2H); MS (ES+) m/z 469.1 (M + 1). Example 4.30 3-[(2-indolyl-5'6-one wind snail [benzo-[l,2-b: 5,4-b']di-p- _3,3'_u5| 哚]- Synthesis of 第三(2Ή)-yl)methyl]tetrahydropyrrole carboxylic acid tert-butyl ester

Displacement of 2-(bromodecyl)tetrahydro-(3-bromomethyl)tetrahydropyrrole-carboxylic acid tert-butyl ester according to the procedure as described in Example 4, and with irrelevant changes 2 such as the bottom of the 'obtained 3-[(2,-keto-5,6-dihydrospiro[benzo-[1,2 seven: 5,4 seven,] one taste 0 south _3'3 卜木]- 1 (2Ή)-yl) fluorenyl] tetrahydro ρ than u each small tickic acid third _ Ding Yu (85%) 'as pale yellow solid: 111] ^ 1 ^ (300 ^ 11 ^, € 0 (: 13 (diastereomerism) δ 7.30 (dd, J = 7.5, 7.5 Hz, 1H), 7.18 (d, J = 7.5 Hz, 1H), 7.07 (dd, J =: 7.2, 6.9 Hz, 1H) , 6.90 (d, J = 7.5 Hz, 1H), 6.46 (s, 1H), 6.42 (s, 1H), 4.91 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H) , 4.54 (t, J = 8.6 Hz, 2H), 3.95-3.44 (m, 3H), 3.41-3.27 (m, 1H), 3.24-3.13 (m, 1H), 3.06-2.92 (m, 2H), 2.82 -2.68 (m, 1H), 2.05-1.92 (m, 1H), 1.82-1.69 (m, 1H), 1.46 (s, 9H), 0.93-0.85 (m, 1H); MS (ES+) m/z 485.3 (M + 23). Example 4.31 143924-sp-20091127-3 -452- (S) 201020257

(2S)-2-[(2·-Mercapto-5,6-dihydrospiro[benzo[1,2-b:5,4-b]difuran, 3,3, Qiao哚]-1 Synthesis of '(2Ή)-yl)methyl]tetrahydropyrrole carboxylic acid tert-butyl ester according to the procedure as described in Example 4.22, and with irrelevant changes, using (S)-2-(toluene) Mercaptooxymethyl)tetrahydropyrrole-indole_carboxylic acid third_butyl vinegar_ (Fuji K. et al., /. Am. C/im. (1989), 111(20): 7921-5) substitution α -Bromo-m-p-benzonitrile-[2S)-2-[(2·-keto-5,6-dihydrospiro[benzo[1,2-b: 5,4,7]]difuran -3,3'-嘀哚]-Γ(2Ή)-yl)fluorenyl] tetrahydropyrrole small carboxylic acid tert-butyl ester (80%), colorless solid: 111]\[]^11(300^ [^, €0 (: 13) (diastereomers) 5 7.37-7.25 (m, 2H), 7.20-7.00 (m, 2H), 6.54-6.41 (m, 2H), 4.96-4.88 (m , 1H), 4.70-4.64 (m, 1H), 4.534 (t, J = 8.6 Hz, 1H), 4.527 (t, J = 8.6 Hz, 1H), 4.31-4.19 (m, 1H), 3.99-3.85 ( m, 1H), 3.80-3.67 (m, 1H), 3.49-3.22 (m, 2H), 3.05-2.91 (m, 2H), 2.10-1.77 (m, 4H), 1.48 (s, 4.5H), 1.42 (s, 4.5H); MS ❹(ES+) m/z 485.1 (M + 23). Example 4.32 4-[(2'-keto-5,6-dihydro [Benzo[i,2-b: 5,4-b,] dicane-3,3'_吲嗓]-Γ(2Ή)-yl)methyl]hexahydropurine--1-reacid Synthesis of tri-butyl ester

According to the procedure as described in Example 4, and the insignificant change was carried out 143924-sp-20091127-3 -453· 201020257 using 4-(indolylsulfonyloxyindenyl)hexahydropyridine-1-carboxylic acid Tri-butyl ester replaces 2-(bromohydrazino)tetrahydro-2H-pyran to give 4-[(2'--yl-5,6-dihydrospiro[benzo[l,2-b:5] ,4-b,]difuran-3,3'-indole]-1,(2Ή)-yl)methyl]hexahydropyridin-1-acidic tert-butyl ester (99%) as a colorless solid :iHNMRQOOMHz'CDCls) &lt;5 7.30 (ddd, J = 7.8, 7.5, 1.2 Hz, 1H), 7.17 (d, J = 7.5 Hz, 1H), 7.06 (dd, J = 7.5, 7.5

Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 6.45 (s, 1H), 6.42 (s, 1H), 4.91 (d, J = 9.〇Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.54 (t, J = 8.6 Hz, 2H), 4.20-4.06 (m, 2H), 3.72 (dd, J = 14.0, 7.5 Hz, 1H), 3.58 (d, J = 14.0, 6.6 Hz, 1H), 3.08-2.92 (m, 2H), 2.75-2.61 (m, 2H), 2.11-1.96 (m, 1H), 1.73-1.60 (m, 2H), 1.45 (s, 9H), 1.33-1.22 (m, 2H) ; MS (ES+) m/z 499.2 (M + 23). Example 4.33 4·-Gasyl-1'-{[5-(Trifluoromethyl)pyran-2-yl]methyl b 5,6-dihydrospiro[Benzo[l,2-b ·· 5 ,4-b']difuran_3,3,-bow|

According to the procedure as described in Example 4, and with irrelevant changes, 4,-gas-based-5,6-dihydrospiro[benzo[12:5,5,7,7]difuran_3,3 was used. ,啕哚]-2,(1Ή)-keto-substituted 5,6-dihydrospiro[benzo-like seven:5,4-7,]difuran_3,3,(4) 哚]-2 (1Ή)-one, And using 2_(bromomethyl)_5•(trifluoromethyl) urethane to replace 2-(bromohydrazino)tetraindole-2H-, to give 4, _ gas group _Γ_{[5 (trifluoro曱基)Neterin-2-yl]methyl b 5,6-dihydrospiro [stupid [12b: 54b,]difuran_3,3,_4 哚]-2(1Η)-one (73%) ' is a colorless solid··melting point 166 169^ ; 1hnmr(3〇〇MHz, CDC13) 5 7.29-7.18 (m, 1H), 7.01 (d, J = 8.2 Hz, 1H), 6.89 (d, J = 143924 -sp-20091127-3 (s) -454- 201020257 7.82 Hz, 1H), 6.74 (d, J = 2.3 Hz, 1H), 6.45-6.34 (m, 2H), 5.11 (d, J = 16.2 Hz, 1H ), 4.99 (d, J = 9.2 Hz, 1H), 4.88 (d, J = 9.2 Hz, 1H), 4.81 (d, J = 16.2 Hz, 1H), 4.52 (t, J = 8.6 Hz, 2H), 2.98 (t, J = 8.60 Hz, 2H); 13 C NMR (75 MHz, CDC13) δ 177.2, 162.2, 162.0, 151.6, 143.1, 141.8 (q, J = 43.0 Hz), 131.6, 130.0, 128.7, 124.6, 118.8 (q, J = 267.1 Hz), 119.7, 118.4, 117.1, 112.7, 109.5, 107.2, 92.9, 77.1, 72.4, 58.2, 37.1, 28.9; MS (ES+) m/z 461.9 (M + 1), 463.9 (M + 1). Example 4.34 © 4'-gas-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Synthesis of difuran-3,3W丨哚]-2'(1Ή)-one

According to the procedure as described in Example 4, and with irrelevant changes, 4·-yl-5,6-dihydrospiro[benzo[i,2-b:5,4-b1]difuran- 3,3'-啕哚]-2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]difuran-3,3,-啕哚]-

2-(Momotylmethyl)tetrahydro-2H-pyrene, 4,-chloro-1,-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo [12_b : 5,4 7 ']difuran _3,3,_ 哚 哚]-2,(1Ή)-ketone (80%) ' is a colorless solid: melting point 78-82 ° C; 4 NMR (300 ΜΗζ, DMSO-d6) 5 7.32-7.09 (m, 1H), 7.05-6.92 (m, 1H), 6.44 (s, 1H), 6.35 (s, 1H), 4.96 (dd, J = 9.1, U Hz, 1H) , 4.85 (d, J = 9.1 Hz, 1H), 4.51 (t, J = 8.7 Hz, 1H), 4.31-4.16 (m, 1H), 4.00-3.59 (m, 1H), 2.98 (t, J = 8.6 Hz, 1H), 2.12-1.80 (m, 1H), 1.76-1.61 (m, 1H); 13C NMR (75 MHz, DMSO-d6) δ 143924-sp-20091127-3 •455· 201020257 178.0 (2), 162.1 (2), 162.0, 144.7, 131.1 (2), 129.8 (2), 128.7 (2), 123.9, 119.4 (2), 118.4 (2), 117.5 (2), 108.1 (2), 92.9, 77.5, 76.9 (2), 72.3, 68.2 (2), 58.1 (2), 44.9 (2), 29.1 (2), 29.0 (2), 25.6 (2); MS (ES+) m/z 397.9 (Μ + 1), 399.9 (M+l). Example 4.45 4·-Bromo-14(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[{,2-b:5,4-b']difuran-3 ,3·-峋哚]-2'(1Ή)-ketone synthesis

4'-Bromo-5,6-dihydrospiro[benzo-[7:5,4-b']difuran-3,3 was used according to the procedure as described in Example 4, and insignificantly changed. ,-,5丨哚]-2'(1Ή)-ketone replaces 5,6-dihydrospiro[benzo-like:b,5,4-b,] two bites. Nanxun]-2"(1Ή)-ketone' and replacement of 2-(bromomethyl)tetrahydro-2H-pipeper with (R)_(tetrahydrofuran-2-yl) decyl 4-methylbenzenesulfonate Methane, 4,-bromo-1,-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[1,2-7:5,4-b,] Furan-3,3,-θ丨哚]-2,(1Ή)-one (75%) ' is a colorless solid: mp 137- 141. 〇; iH NMR (300 ΜΗζ, DMSO-dg) (diastereomers) ) 5 7 3〇_7.1〇(m,3Η), 6.42-6.37 (m,1Η), 6.32 (s, 1H), 4.88 (d, J = 9.63 Hz, 1H), 4.70-4.63 (m, 1H) , 4.46 (t, J = 8.6 Hz, 2H), 4.18-4.05 (m, 1H), 3.85-3.52 (m, 4H), 2.93 (t, J = 8.5 Hz, 2H), 2.01-1.67 (m, 3H) ), 1.64-1.49 (m, 1H); 13C NMR (75 MHz, DMSO-d6) 5 177.5 (2), 162.2, 161.8, 145.7, 130.9, 130.2 (2), 126.6, 119.9 (2), 119.0 (2 ), 118.9 (2), 118.1, 92.5, 77.5, 76.3, 76.1, 72.5, 67.7 (2), 65.4, 58.7, 44.5, 29.0 (2), 28.7, 25.5; MS (ES+) m/z 443.9 (M + 1), 445.9 (M+l) ° 143924-sp-20091127-3 *456- 201020257 Example 4.36 Γ-(3-Methylbutyl)-2,3-dihydrospiro[味和[2,3_g][1,4 Benzodioxene terpene ^ ]-2\ r¥L)-m ^ ^ ^

According to the procedure as described in Example 4, and irrelevant changes were made, φ used 2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3,-♦Duo]-2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzop,2-b:5,4-b,]difuran_3,3,-吲哚]- 2&quot;(1Ή)-ketone, and the replacement of 2-(bromomethyl)tetrahydro-2-indole-pentanol with 1-bromo-3-methylbutane to obtain Γ-(3-methylbutyl) _2,3_Dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8 吲哚]-2|(1Ή)-one (64%), Colorless solid: mp 134-137 ° C (hexanes); 1H NMR (300 MHz, CDC 13) 6 7.30 (ddd, J = 7.7, 7.7, 1.3 Hz, 1H), 7.15 (dd, J = 7.2, 0.9 Hz, 1H), 7.03 (ddd, J = 7.4, 7.4, 0.7 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.20 (s, 1H), 4.88 (d, J = 9.0 Hz, φ 1H), 4.62 (d, J = 9.0 Hz, 1H), 4.21-4.16 (m, 2H), 4.14-4.09 (m, 2H), 3.89-3.80 (m, 1H), 3.73-3.63 (m, 1H), 1.75-1.59 (m, 3H), 1.00 (d, J = 6.3 Hz, 6H); 13C NMR (75 MHz, CDC13) ά 177.3, 155.4, 144.6, 142.5, 138.3, 132.8, 128.9, 124.0, 123.2, 121.3, 111.6, 108.6, 99.4, 80.2, 64.6, 64 . . . . . . . . . . . . . . . 3.83; Found: C, 72.21; H, 6.31; N, 3.55. Example 4.37 143924-sp-20091127-3 -457· 201020257 Γ-(tetrahydro-2H-t-label-4-ylindenyl)_2,3-dihydrospiro[吱,[2,3_g][1, 4] Synthesis of benzodioxanthene-8,3'-吲哚]-2|(1Ή)-one

According to the procedure as described in Example 4, and irrelevant changes were made, 2,3-dihydrospiro[pf-pyrano[2,3-g][i,4]benzodioxanthene was used. ]_ 2|(1 condition)-keto-substituted 5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3,3,-吲哚]-2"(1Ή) -ketone, and using 4-(exylmethyl)tetrahydro-2Ημ trace to replace 2-(bromomethyl)tetrahydro-2Η-«, to obtain 1'-(tetrahydro-2Η-jum- 4-ylindenyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,_啕哚]-2, ( 1Ή)-net (95%) as colorless solid: mp 129-131 ° C (hexane); 1H NMR (300 MHz, CDC13) &lt;5 7.29 (ddd, J = 7.9, 7.9, 1.3 Hz, 1H) , 7.16 (d, J = 7.5 Hz, 1H), 7.04 (ddd, J = 7.4, 7.4, 1.0 Hz, 1H), 6.89 (d, J = 8.1 Hz, 1H), 6.50 (s, 1H), 6.18 ( s, 1H), 4.87 (d, J = 8.9 Hz, 1H), 4.62 (d, J = 8.9 Hz, 1H), 4.22-4.16 (m, 2H), 4.15-4.09 (m, 2H), 4.03-3.94 (m, 2H), 3.74 (dd, J = 13.8, 7.7 Hz, 1H), 3.55 (dd, J = 13.8, 7.1 Hz, 1H), 3.42-3.30 (m, 2H), 2.20-2.03 (m, 1H) ), 1.66-1.56 (m, 2H), 1.53-1.40 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 177.8, 155.4, 144.7, 142.8, 138.4, 132.5, 128.9, 124.2, 123.4, 121.1, 111.5, 108.7, 99.5, 80.4, 67.6, 67.5, 64.6, 64.0, 58.1, 46.2, 34.0, 30.93, 30.86; MS (ES+) m/ z 394.2 (M + 1); Calculated for C23H23N05: C, 70.21; H, 5.89; N, 3.56; found: C, 70.15; H, 5.92; N, 3.20. Example 4.38 Γ-(tetrahydro- 2H-Buran-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzo 143924-SP-20091127-3 -458- 201020257 Dioxane Synthesis of terpene-8,3'-蚓哚]-2Χ1Ή)-one

According to the procedure as described in Example 4, and irrelevant changes were made, 2,3-a snail [吱0南和[2,3-g][l,4]benzodioxanthene- 8,3'-ρ 嗓]-2'(1Ή)-ketone replacement 5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲嗓]·2"(1Ή)-ketone, obtaining ι'_(tetrahydro-2H-methane-2-ylindenyl)-2,3-dihydrospiro[吱® benzo benzodioxanthine Alkene-8,3·-吲哚]-2,(1Ή)-one (45%) as colorless solid: mp 158-166°C (hexanes); 1H NMR (300 MHz, CDC13) Isomers δ 7.31-7.25 (m,1H), 7.13 (d, J = 7.5 Hz, 1H), 7.08-7.00 (m, 2H), 6.48 (s, 1H), 6.24 (s, 0.5H), 6.22 (s, 0.5H), 4.89 (d, J = 9.0 Hz, 0.5H), 4.88 (d, J = 9.0 Hz, 0.5H), 4.64 (d, J = 9.0 Hz, 0.5H), 4.63 (d , J = 9.0 Hz, 0.5H), 4.21-4.16 (m, 2H), 4.14-4.09 (m, 2H), 4.01-3.93 (m, 1H), 3.91-3.82 (m, 1H), 3.74-3.63 ( m, 2H), 3.44-3.33 (m, 1H), 1.91-1.81 (m, 1H), 1.68-1.31 _ (m, 5H) ; 13C NMR (75 MHz, CDC13) (diastereomer) δ 177.89, 177.80, 155.30, 155.27, 144.61, 143.25, 143.11, 138.34, 132.46, 132.35, 128 .78, 128.73, 123.66, 123.64, 123.19, 123.17, 121.51, 121.45, 111.76, 111.62, 109.90, 109.77, 99.41, 99.36, 80.14, 75.75, 75.58, 68.57, 68.53, 64.63, 64.02, 58.08, 58.04, 45.83, 45.77 , calcd for C23H23N05: C, 70.21; H, 5.89; N, 3.56; found: C, 70.03; H, H,,,,,,,,,,,,,,,,,,,,,, , 5.97; N, 3.17. Example 4.39 Γ-[(5-Alkyl-1-methyl-1H-imidazol-2-yl)methyl]-2,3-dihydrospiro[味喃和143924-sp-20091127-3 -459- 201020257 Synthesis of [2,3-g][l'4]benzodioxolene _8,3,_巧哚]

According to the procedure as described in Example 4, and the insignificant change was made, 2,3-dihydrospiro[c-buto[2,3-g][l,4] benzodioxanthene -8 was used. ,3,_吲哚]_ 2χΓΗ)--substituted 5,6-dihydrospiro [benzo-like: b, 5,4,7,]difuran-3,3,-吲哚]-2" (1Ή) - hydrazine, and 5-(chloromethyl)-1-methyl-1H-imidazole hydrochloride was used to replace 2-(bromomethyl)tetrahydro-2 hydrazine - sulphonate to obtain r- [(5-Gas-indole-methyl-1Η-imidazol-2-yl)methyl]-2,3-dihydrospiro[pf-pyrano[2,3-g][l,4]benzo Dioxogene-8,3'-indole]-2'(1Ή)-one (94%) as colorless solid: m.p. 91-95. (3 (dioxane); 1H NMR (300 MHz , CDC13) &lt;5 7.39 (d, J = 7.8 Hz, 1H), 7.27 (ddd, J = 7.7, 7.7, 1.2 Hz, 1H), 7.14 (dd, J = 7.2, 0.9 Hz, 1H), 7.05 ( Ddd, J = 7.4, 7.4, 0.8 Hz, 1H), 6.94 (s, 1H), 6.50 (s, 1H), 6.18 (s, 1H), 5.12 (d, J = 15.6 Hz, 1H), 4.93 (d , J = 15.6 Hz, 1H), 4.87 (d, J = 9.0 Hz, 1H), 4.62 (d, J = 9.0 Hz, 1H), 4.21-4.16 (m, 2H), 4.13-4.08 (m, 2H) , 3.59 (s, 3H) ; 13C NMR (75 MHz, Q CDC13) δ 177.3, 155.4, 144.8, 141.9, 141.7, 138.5, 131.6, 129.3, 124.8, 124.0, 123.8, 120.7, 119.5, 111.5, 110.7, 99.6, 80.3, 64.6, 64.0, 58.1, 38.2, 31.0 ; MS (ES+) m/z 426.2 (M + 1), 424.2 ( M + 1). Example 4.40 1·_[(5_Alkyl-1-indenyl-1Η-_ &gt;»Shen-2-yl)methyl]-2,3-dihydrospiro [p-aramid [2,3-§][1,4] Synthesis of benzodioxanthene-8,3'-4丨嗓]-2'(1 ugly)-ketohydrochloride 143924-SP-20091127-3 •460- 201020257

Γ-[(5-Alkyl-1-methyl-1H-imidazol-2-yl)methyl]-2,3-dihydro was used according to the procedure as described in Example 2.28, and the insignificant change was applied. Snail [bite and drink [2,3-g][l,4] Ben and a milky land thinner -8,3'-p bow 丨嗓]-2*(1'H)-嗣 replacement 1-曱Γ-Γ-{[5-(trifluoromethyl)-pyran-2-yl]hydrazino 2,3-dihydro-1H-spib- bromo[3,2-g] φ [Μ]benzene And p-cultivated -8,3·- 哚 哚]-2'(1Ή)-ketone, obtained Γ-[(5-alkyl small methyl-1H_imidazol-2-yl)indenyl]-2,3- Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-吲嗓]-2' (ΓΗ&gt; ketone hydrochloride (82%), Colorless solid: 207-208 ° C (hexane); 4 NMR (300 MHz, DMSO-d6) &lt;5 7.80 (s, 1H), 7.40 (d, J = 7.8 Hz, 1H), 7.31 (dd, J = 7.8, 7.2 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.08 (dd, J = 7.5, 7.2 Hz, 1H), 6.50 (s, 1H), 6.42 (s, 1H), 5.30 (s, 2H), 4.83 (d, J = 9.6 Hz, 1H), 4.66 (d, J = 9.6 Hz, 1H), 4.20-4.15 (m, 2H), 4.13-4.08 (m, 2H), 3.70 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.0, 154.8, 144.2, 141.8, 141.7, 〇137.9, 132.1, 128.6, 123.6, 123.5, 121 .0, 120.9, 118.0, 111.9, 109.8, 98.6, 79.9, 64.2, 63.6, 57.3, 35.8, 31.9 ; MS (ES+) m/z 426.2 (M + 1), 424.2 (M + 1); for C22H18C1N304 · Ha · calcd for H20: C, 55.24; H, 4.43; N, 8.78; found: C, 55.51; H, 4.18; N, 8.58. Example 4.41 1,-(acridin-2-ylindenyl)- 2,3-Dihydrospiro['1f- s-[2,3-8][1,4]benzodioxolene-8,3^5 pulo]-2'(1Ή)-ketone Synthesis 143924-sp-20091127-3 -461- 201020257

According to the procedure as described in Example 4, and irrelevant changes were made, 2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxolene-8,3 was used. , _吲嗓]-2'(1Ή)-ketone replacement 5,6-dihydrospiro[benzo[||, i,2_b: 5,4,7,]difuran_3,3,_ρ?丨嗓]-2&quot (1Ή)-鲷' and 2-((hydrazinyl)tetrahydro-2H-pyranate was replaced with 2-(Mo-methyl)P-pyridyl hydrobromide to obtain Γ_(pyridine-2-yl fluorenyl) )_2 3_Dihydrospiro [smell and [2,3-g][l,4]benzodioxanthene_8,3,_10]_2, (__ketone (8〇%) , as a colorless solid: mp 208-209 ° C (hexanes); 1H NMR (300 MHz, CDC13) 5 8.58 (d, J = 4.8 Hz, 1H), 7.65 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.28-7.15 (m, 4H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.31 (s, 1H) ), 5.21 (d, J = 16.0 Hz, 1H), 4.97 (d, J = 16.0 Hz, 1H), 4.96 (d, J = 8.7 Hz, 1H), 4.68 (d, J = 8.7 Hz, 1H), 4.22-4.17 (m, 2H), 4.15-4.10 (m, 2H) ; 1 3C NMR (75 MHz, CDC13) &lt;5 177.6, 155.6, 155.3, 149.6, 144.6, 142.2, 138.3, 137.1, 132.2, 128.9, 123.8, 123.5, 122.8, 121. 6, 121.1, 111.8, 109.6, 99.4, 80.2, 64.5, 63.9, 58.2, 46.1; MS (ES+) m/z 387.2 (M+l). Example 4.42 l'_(P-pyridyl_2_yl fluorenyl) -2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene-8,3'-thirsty]-2'(1Ή)-ketohydrochloride Synthesis of salt

According to the procedure as described in Example 2.28, and irrelevant changes were made, 143924-sp-20091127-3 -462- 201020257 using Γ-0-pyridin-2-ylmethyl)-2,3-dihydrospiro [ Benzo-benzodioxanthene-8,3W丨哚]-2·(1Ή)-ketone replacement 1-methyl(trifluoromethyl)methane-2-yl]methyl}-2,3 -Dihydro-1Η-spiro[吱,[3,2-g][l,4]benzoxazino_8,3,-&lt; 哚]-2'(1Ή)-one, obtained Γ-( Pyridin-2-ylmethyl)_2,3-dihydrospiro[吱,[2,3-Lu][1,4]benzodioxanthene -8,3'-'»5 卜朵] -2' (1 ugly)-ketohydrochloride (89%), as a light-colored powder. Melting point 206-208 C (hexane); 1H NMR (300 ΜΗζ, DMSO-d6) δ 8.68 (dd, J = 4.8, 0.9 Hz, 1H), 8.13 (ddd, J = 7.7, 7.7, l.〇Hz, 1H), 7.65-7.58 (m, 2H), 7.26 (ddd, J = 7.7, 7.7, 1.1 Hz, 1H) , 7.19 (d, J = 7.2 β Hz, 1H), 7.07-7.01 (m, 2H), 6.51 (s, 1H), 6.35 (s, 1H), 5.24 (d, J = 17.1 Hz, 1H), 5.17 (d, J = 17.1 Hz, 1H), 4.83 (d, J = 9.3 Hz, 1H), 4.70 (d, J = 9.3 Hz, 1H), 4.21-4.16 (m, 2H), 4.14 - 4.09 (m, 2H); 13 C NMR (75 MHz, DMSO-de) &lt;5 177.0, 154.7, 153.5, 146.2, 144.2, 142.2, 141.2, 137.8, 131.9, 128.8, 124.2, 123.6, 123.23, 123.21, 121.2, 111.7, 109.3, 98.7, 79.5, 64.2, 63.6, 57.3, 43.3; MS (ES+) m/z 387.2 (M + 1); for c2 For C, 64.42; H, 4.62; N, 6.53; found: c, 64.72; H, 4.55; N, 6.13.实例 Example 4.43 r-[(2S)-Tetrahydrofuran-2-ylindenyl]_2,3 di argon [furan [2,3_g][14] benzodioxanthene-8,3'-吲哚]-2,(1Ή)-ketone synthesis

According to the procedure as described in Example 4, and irrelevant changes were made, 2,3-dihydrospiro[唉-dioxoamphet- 8,3,-吲143924-sp-20091127-3 - 463- 201020257 哚]-2' (1 ketone-keto-substituted 5,6-dihydrospiro[benzo[1,2-7:5,4-7']difuran-3,3'-吲哚]-2· · (1Ή)-ketone, and replacing 2-(bromomethyl)tetrahydro-2H-pyran with (3)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate to obtain r_[(2S) -tetrahydrofuran-2-ylmethyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3'-thirsty]-2Χ1Ή )-ketone (69%) as colorless solid: mp 173 - 175 ° C (methanol); 4 NMR (300 MHz, CDC13) (diastereomers) (5 7.32-7.25 (111,111), 7.16 -7.00 (m, 3H), 6.49 (s, 1H), 6.24 (s, 1H), 4.88 (d, J = 8.9 Hz, 1H), 4.63 (d, J = 8.9 Hz, 1H), 4.31-4.22 ( m, 1H), 4.21-4.17 (m, 2H), 4.14-4.09 (m, 2H), 3.99-3.67 (m, 4H), 2.09-1.66 (m, 4H); 13 C NMR (75 MHz, CDC13) (diastereomers) (5 178.1, 177.9, 155.3, 144.6, 143.0, 142.9, 138.4, 132.4, 132.3, 128.9, 128.8, 123.8, 123.7, 123.3, 121.4, 121. 3, 111.7, 111.6, 109.8, 109.5, 99.4, 80.3, 80.2, 77.1, 76.8, 68.35, 68.31, 64.6, 64.0, 58.09, 58.06, 44.7, 29_4, 29.0, 25.9, 25.7; MS (ES+) m/z 380.2 (Μ + 1). Example 4.44 14(2R)-Tetrahydrofuran-2-ylindenyl]_2,3-dihydrospiro[furo[2,3-phan [1,4]benzodioxanthene- Synthesis of 8,3'-吲哚]-2,(1Ή)-ketone

According to the procedure as described in Example 4, and irrelevant changes were made, 2'3_dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8 was used. ,3,_w哚]_ 2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[u-7:5 4 七,]二咬喃_3,3,_十朵]_ 2 (1 H)-ketone, and replacing 2-(bromomethyl)tetrahydro-2H-pyran with 4-methylbenzenesulfonic acid (8)-(tetrahydrofuran-2-yl)methyl ester to obtain r [(2R)_rahydrofuran· 2基曱143924-sp-20091127-3 (S) -464- 201020257 base]-2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxanthene -8,3·-啕哚]-2'(1Ή)-one (55%) as a colorless solid: m.p. s. s. 176. (hexane); iHNMR (300 MHz, CDC13) 5) 7.32-7·25 (m, 1H), 7.16-7.00 (m, 3H), 6.49 (s, 1H), 6.24 (s, 1H), 4.88 (d, J = 8.7 Hz, 1H), 4.63 (d, J = 8.7 Hz, 1H), 4.31-4.22 (m, 1H), 4.21-4.17 (m, 2H), 4.14-4.09 (m, 2H), 3.99-3.67 (m, 4H), 2.09-1.82 (m, 3H), 1.78-1.66 (m, 1H); 13C NMR (75 MHz, CDC13) ( diastereomers) 6 178.1, 177.9, 155.3, 144.6, 143.0, 142.9, 138.4, 132.4, 132.3, 128.9, 128.8, 123.8, 123.7, 123.3, 121.4, 121.3, 111.7, 111.6, ® 109.8, 109.5, 99.4, 80.29, 80.26, 77.1, 76.8, 68.4, 68.3, 64.6, 64.0, 58.10, 58.08, 44.7, 29.4, 29.1, 25.9, 25.7 ; MS (ES+) m /z 380.2 (M + 1) 〇Example 4.45 1'-(1,4-Dioxo-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-幻[1 ,4] Synthesis of benzodioxanthene-8,3W丨哚]-2\1Ή)-one

2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-2'(1Ή)-one (0.30克' 1.03 mmol, 2-(4-methyl)-1,4-dioxene (0.31 g ' 1.35 mmol) and carbonate planer (0.52 g, 1.58 mmol) in 2-butyl The mixture in ketone (7 mL) was stirred under reflux with nitrogen for 4 h. Once cooled, the reaction was immediately diluted with ethyl acetate and the suspension was filtered and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by flash column chromatography eluting with m. m. Methyl)-2,3-dihydrospiro[[,,,,,,,,,,,,, An inseparable mixture of decylamine (0.36 g). Then, this material, a mixture of benzyl bromide (〇12 ml, 丨(8) mmol) and carbonic acid (0.50 g, 1.55 mmol) in 2-butanone (7 ml), under reflux and nitrogen Stir for 15 hours. Purified as described above, and purified by flash column chromatography (hexane / ethyl acetate) (2:1, to 1:1) to obtain Γ-(1,4-oxo-orbital-2-曱))-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one (0.24 g, 58%), as a colorless solid, with y-benzyl-2,3-dihydrospiro[[,,,,,,,,,,,,,,,,,,, , 3, _ 哚 哚] - 2' (1 Ή)-ketone (0.09 g, 24%), as a colorless solid. About r_(1,4_dioxosindol-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3_β][1,4] benzodioxanthene-8 , 3·-蚓哚]-2·(1Ή)-ketone characteristic performance: melting point i6〇_165〇c (hexane); η NMR (300 MHz, CDC13) (diastereomer) occupies 7.26-7.34 (m, 1 Η), 7.16 (d, J = 7.5 Hz, 1H), 7.01-7.09 (m, 2H), 6.49 (s , 1H), 6.24 (s, 0.5H), 6.21 (s, 0.5H), 4.88 (d, J = 8.9 Hz, 0.5 Hz), 4.87 (d, J = 8.9 Hz, 0.5H), 4.64 (d, J = 8.9

Hz, 0.5H), 4.63 (d, J = 8.9 Hz, 0.5H), 4.22-4.16 (m, 2H), 4.15-4.09 (m, 2H), 3.99-3.78 (m, 4H), 3.76-3.55 ( m, 4H), 3.47-3.37 (m, 1H); 13C NMR (75 MHz, CDC13) (diastereomer) &lt;5 177.9, 177.8, 156.3, 155.3, 144.71, 144.69, 142.72, 142.66, 138.42, 138.39, 132.4, 132.3, 128.91, 128.85, 123.9, 123.8, 123.5, 121·3, 121.1, 111.7, 111.6, 109.6, 109.4, 99.49, 99.46, 80.2, 80.0, 73.32, 73.29, 69.4, 69.2, 66.8, 66.7, 66.52, 66.48, 64.6, 64.0, 58.1, 58.0, 41.85, 41.76; MS (ES+) m/z 396.2 (Μ + 1). Example 4.46 1'-(3,4-Dimethoxybenzyl)-2,3-dihydrospiro 1&gt; Des-[2,3-2][1,4]benzodioxanthene- Synthesis of 8,3^吲哚]-2·(1Ή)-ketone 143924-sp-20091127-3 -466-

201020257

According to the procedure as described in Example 4, and irrelevant changes were made, 2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxolene-8,3 was used. ,峋哚]-2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[12-7:5 4-7,]difuran_3 3,_p5丨哚]-2&quot;(ΓΗ)-ketone And using dimethoxybenzyl bromide (〇guri, τ et al., c/^. PA_· (1977), 25: 2287-91) to replace 2-(Momotyl)tetrahydro-2H-flavor喃, ® obtained Γ_(3,4-dimethoxybenzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8 , 3'-啕哚]-2'(1Ή)-one (100%) as colorless solid: mp 209-211 ° C (hexane / ether); 1H NMR (300 MHz, CDC13) 5 7.23-7.14 ( m, 2H), 7.01 (dd, J = 7.5, 7.5 Hz, 1H), 6.92-6.80 (m, 4H), 6.51 (s, 1H), 6.21 (s, 1H), 5.09 (d, J = 15.3 Hz , 1H), 4.94 (d, J = 9.0 Hz, 1H), 4.68 (d, J = 15.3 Hz, 1H), 4.67 (d, J = 9.0 Hz, 1H), 4.22-4.16 (m, 2H), 4.13 -4.08 (m, 2H), 3.86 (s, 3H), 3.84 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 177.7, 155.3, 149.5, 148.8, 144.7, 142.2, 138.4, 132.4, 128.9, 128.4 , 124.0, 123.5, 121.3, 12 0.0, ® 111.5, 111.2, 110.5, 109.5, 99.6, 80.1, 64.6, 64.0, 58.2, 56.02, 55.99, 44.1 ; MS (ES+) m/z 446.0 (M + 1) ° Example 4.47 1,_(3,5 -dimethoxybenzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-呻哚]-2 ·(1Ή)-_ Synthesis 143924-sp-20091127-3 -467- 201020257

Using 2,3-dihydrospiro[吱,[2,3_g][1,4;^and dioxererene_8,3,,丨哚]_ 2'(1)-嗣, 5, 6-Dihydrospiro[benzo[1,2-7:5,4-7,]difuran_3,3,_one to]_ 2"(1Ή)-one, and 3,5-dimethoxy Barium bromide is substituted for 2 (bromomethyl)tetrahydro-2 fluorene-anthracene to obtain 1'-(3,5-dimethoxybenzyl)-2,3 dihydrospiro [biting and argon [2,3 g] [1,4] benzodioxanthene _8,3,_p5丨哚]_21 (11-ketone (97%), as colorless solid: mp 192-195 ° C (diethyl ether / hexane); 1 η nmR (300 MHz, CDCl3) 5 7 23 7 15 (m, 2H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 6.81 (d, J = 7.5 Hz, 1H), 6.51 (s, 1H), 6.47 (d, J = 1.8 Hz, 2H), 6.37 (t, J = 1.8 Hz, 1H), 6.25 (s, 1H), 5.04 (d, J = 15.5 Hz, 1H), 4.95 (d, J = 9.0 Hz, 1H), 4.72 (d, J = 15.5 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.22-4.16 (m, 2H), 4.14-4.09 (m, 2H), 3.76 (s, 6H) ; 13 C NMR (75 MHz, CDC13) δ 177.7, 161.3, 155.4, 144.7, 142.2, 138.5, 138.2, 132.3, 129.0, 123.9, 123.5, 121.2, 111.6, 109.5, 105.4, 99.8, 99.6 , 80.2, 64.6, 64.0, 58.2, 55.5, 44.3; MS (ES+)m/z 446.0 (M+l) 〇Example 4.48 1·-(2,3-Diazin-1,4-benzodioxanthracene-6-ylmethyl)-2,3-dihydrospiro[p lost b South Synthesis of [2,3$][1,4]benzodioxanthene-8,3,-啕哚]-2'(1,11)-one

〇· 143924-sp-20091127-3 •468- 201020257 Follow the procedure as described in Example 4 and perform irrelevant changes using 2,3-dihydrospiro[吱,[2,3-g][ l,4]benzodiazepines _8,3,_4丨哚]_ 2(1 H)-嗣 substitution 5,6-one wind snail [benzoquinone [l,2-b : 5,4- b']ji·bite _3,3'-p5|p to]_ 2 (1H)-ketone, and use 6-(bromomethyl)-2,3-dihydrobenzo[1,4 Dioxetene (Capilla, AS et al., (2〇〇1), 57: 8297-304) displaces 2-(bromomethyl)tetrahydro-2H-pyran' to obtain Γ-(2,3 -dihydro-l,4-benzodioxanthene _6_ fluorenyl)-2,3-dihydrospiro[p-f-[2,3-g][l,4]benzodiox陆8稀_8,3,_ 哚 哚]-2'(1Ή)-ketone (100%), colorless solid: melting point 12〇123 art (hexane/ethyl ether), 1H NMR (300 Hall 2, CDC13) 5 7.20 (ddd, J = 7.8, 7.5, 1.2 Ηζ, 1 Η), 7.15 (dd, J = 7.4, 0.8 Hz, 1H), 7.01 (ddd, J = 7.5, 7.4, 0.7 Hz, 1H), 6.85 -6.79 (m, 4H), 6.50 (s, 1H), 6.24 (s, 1H), 4.93 (d, J = 8.7 Hz, 1H), 4.92 (d, J = 15.5 Hz, 1H), 4.76 (d, J = 15.5 Hz, 1H), 4.65 (d, J = 8.7 Hz, 1H), 4.23 (s, 4H), 4. 22-4.17 (m, 2H), 4.14-4.10 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.5, 155.4, 144.7, 143.8, 143.3, 142.3, 138.4, 132.4, 129.0, 128.9, 123.9, 123.4 , 121.2, 120.5, 117.8, 116.5, 111.8, 109.5, 99.5, 80.4, 64.6, 64.44, 64.41, 64.0, 58.2, 43.8; MS (ES+) m/z 444.0 (M + 1). Example 4.49 (R)-l'-{[5-(Trifluoromethyl) succinyl-2-yl] fluorenyl}-2,3-dihydro snail [bit succinyl[2,3-g][l ,4] Synthesis of benzodioxanthene _8,3'_啕哚]_2'(1Ή)__

According to the procedure as described in Example 4, and irrelevant changes were made, (R)-(2,3-dihydrospiro[,2,3-g][1,4]benzodioxane was used.圜 圜 _8,3, _ _ _ 924924-SD-20091127-3 201020257 哚]-2' (1 ugly)-ketone replacement 5,6-dihydrospiro [benzo[1,2 seven: 5,4 seven ']difuran-3,3,-啕哚]-2"(1Ή)-one, and 2-(bromodecyl)-substituted 2-(bromoindenyl)-5-(trifluoromethyl)furan Tetrahydro-2 hydrazine-pyran to obtain (R)-r-{[5-(trifluoromethyl) hexane-2-yl]methyl}-2,3-dihydrospiro[吱 并[2 , 3-g][l,4]benzodioxanthene _8,3,-呻哚]-2\1Ή)- Stuffed (92%), colorless solid: melting point 64-68 ° C ( Methanol/water); 1 NMR (300 MHz, CDC13) δ 7.30 (ddd, J = 7.8, 7.7, 1.0 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.07 (dd, J = 7.5, 7.2 Hz, 1H), 6.99 (d, J = 8.1 Hz, 1H), 6.76-6.72 (m, 1H), 6.50 (s, 1H), 6.38 (d, J = 3.3 Hz, 1H), 6.19 (s, 1H), 5.06 (d, J = 16.5 Hz, 1H), 4.89 (d, J = 16.5 Hz, 1H), 4.90 (d, J = 9.0 Hz, 1H), 4.64 (d, J = 9.0 © Hz, 1H ), 4.22-4.16 (m, 2H), 4.14-4.09 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.2, 155.3, 152.2, 144.8, 141.8 (q, J = 43.0 Hz), 141.5, 138.5, 132.2, 129.1, 124.2, 123.9, 120.9, 118.9 (d, J = 267 Hz), 112.8 (d, J = 2.8 Hz), 111.6, 109.3, 109.0, 99.5, 80.1, 64.6, 64.0, 58.1, 37.1; MS (ES+) m/z 443.9 (M+l). Example 4.50 (8)-[-{[5-(Trifluoromethyl)pyran _2-yl] fluorenyl 2,3-dihydrospiro-[2,3-g][l,4]benzodioxolene _8,3,_+tomato]_2, (1Ή Synthetic

According to the procedure as described in Example 4, and irrelevant changes were made, (S)-(2,3-dihydrospiro[2,3414]benzodioxene _8 3, _吲木]-2(1H)-鲷 Replacement 5,6-dihydrospiro [benzo[i,2_b : 5,4 seven'] dipyran-3,3W| 11 wood]-2 (1 Η) -ketone' and the use of 2-(bromohydrazino)_5-(trifluoromethyl) succinyl substituted 143924-sp-20091127-3 470 (S) 201020257 2-(Momotylmethyl)tetrahydro-2H-piperider To obtain (S)-l'-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l , 4] benzodioxanthene _8,3,_, 哚]-2'(1Ή)-one (95%), colorless solid: melting point 53-56 ° C (furfuryl alcohol / water); iH NMR (300 MHz, CDC13) δ 7.30 (dd, J = 7.8, 7.8 Hz, 1H), 7.18 (d, J = 7.2 Hz, 1H), 7.08 (dd, J = 7.5, 7.5 Hz, 1H), 6.99 ( d, J = 8.1 Hz, 1H), 6.74 (dd, J = 2.1, 0.9 Hz, 1H), 6.50 (s, 1H), 6.38 (d, J = 3.0 Hz, 1H), 6.19 (s, 1H), 5.06 (d, J = 16.2 Hz, 1H), 4.90 (d, J = 9.0 Hz, 1H), 4.89 (d, J = 16.2 Hz, 1H), 4.64 (d, J = 9.0 Hz, 1H), 4.22- 4.17 (m, 2H), 4.14-4.09 (m, 2H); 13 C NMR (75 MHz, ❹ CDC13) (5 177.2, 155. 3, 152.2, 144.8, 141.8 (q, J = 43.0 Hz), 141.5, 138.5, 132.2, 129.1, 124.2, 123.9, 120.9, 118.9 (q, J = 267 Hz), 112.8 (q, J = 2.8 Hz), 111.6, 109.3, 109.0, 99.5, 80.1, 64.6, 64.0, 58.1, 37.1; MS (ES+) m/z 443.9 (M+l). Example 4.51 (S)-r-(pyridin-2-ylindenyl)- Synthesis of 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3·-吲哚]-2·(1Ή)-one

According to the procedure as described in Example 4, and irrelevant changes were made, using (S)-2,3-dihydrospiro|&gt; Furano[2,3-g][i,4]benzoic Oxygen decene-8,3,- 哚 哚]-2Χ1Ή)-ketone replacement 5,6-dihydrospiro[benzopyrene:5,4-b']difuran-3,3W丨嗓]-2 ··(1Ή)-ketone' and (2-)-r-7-pyridinyl using 2-(Molylmethyl-cyclohexane arbrate to replace 2-(bromo-mercapto)tetrahydro-2-indole-L. 2-ylindenyl)-2,3-dihydrospiro[aceto[2,3-g][l,4]benzodioxene _8,3,_吲哚]_2'(ΓΗ ) ketone (95%), 143924-sp-20091127-3 • 471 - 201020257 colorless solid: melting point 144-146 ° C (diethyl ether / hexane); 4 NMR (300 MHz, CDC13) (5 8.59 (dd, J = 5.1, 0.6 Hz, 1H), 7.73 (ddd, J = 7.8, 7.5, 1.5 Hz, 1H), 7.33-7.27 (m, 2H), 7.22 (ddd, J = 7.7, 7.7, 1.3 Hz, 1H) , 7.17 (dd, J = 7.4, 0.9 Hz, 1H), 7.03 (ddd, J = 7.5, 7.5, 0.9 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.29 (s, 1H), 5.26 (d, J = 15.9 Hz, 1H), 5.04 (d, J = 15.9 Hz, 1H), 4.96 (d, J = 9.0 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.22-4.18 (m, 2H), 4.15-4.11 (m, 2H); 13C NMR (75 MHz, CDC13) &lt;5 177.7, 155.4, 155.3, 148.6, 144.8, 142.0, 138.4, 138.2, 132.2, 129.0, 124.0, 123.7, 123.3, 122.3, 121.1, 111.8, 109.7, 99.5, 80.3, 64.6 , 64.0, 58.2, 45.5; MS (ES+) m/z 387.0 (M + 1). Example 4.52 Γ-0»pyridin-2-ylmethyl)-6,7-dihydrospiro[benzo[l, Synthesis of 2-b: 4,5-b,]difuran-3,3^丨哚丨哚]-2\1Ή)-ketone

According to the procedure as described in Example 4, and with irrelevant changes, 6,7-dihydrospiro[benzo[i,2-b:4,5-b,]difuran-3,3,- Μ丨哚]-2,(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[i,2_b: 5,4,7,]dioxin-3,3Wbdu]-2,,(1Ή )-ketone, and using 2-(exylmethyl(tetra)pyridine hydrobromide to displace 2 (bromomethyl)tetrahydro-2-indole_yield' to obtain 1'-(latyridin-2-ylmethyl)- 6,7-Dihydrospiro[benzo[i,2-b:4,5-b,]difurin-3,3-θ丨嗓]-2'(1Ή), (67%), colorless Solid: melting point 198_2 〇〇. 〇 (B puzzle / hexane); 1H NMR (3 〇〇 MHz, CDC13) δ 8.59 (d, J = 4.8 Ηζ, 1 Η), 7.71 (dd, J = 7.8, 7.5 Hz, 1H), 7.32-7.15 (m, 4H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 6.94 (d, J = 7.8 Hz, 1H), 6.82 (s, 1H), 6.17 (s, 1H) ), 5.27 (d, J = 15.6 Hz, 1H), 143924-sp-20091127-3 201020257 5.01 (d, J = 15.6 Hz, 1H), 4.98 (d, J = 9.0 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.49 (td, J = 8.7, 0.7 Hz, 2H), 3.15 (t, J = 8.7 Hz, 2H); 13 C NMR (75 MHz, CDC13) &lt;5 177.7, 155.3, 155.2, 154.9, 148.6, 142.1, 138.3, 132.1 , 129.1, 128.9, 127.6, 124.0, 123.7, 123.3, 122.3, 109.7, 107.2, 104.0, 80.1, 71.8, 58.6, 45·5, 30.4; MS (ES+) m/z 370.9 (M + 1). Example 4.53 l Synthesis of '-[(2R)-tetrahydrofuran-2-ylmethyl]-6,7-dioxin-5H-spiro[furo[3,2-g]nonene_3,3'-吲嗓] ketone

According to the procedure as described in Example 4, and with irrelevant changes, 6,7-dihydro-5-indole-[3,2-gK-ene-3,3,-啕哚]-2 was used. , (1Ή)-keto-substituted 5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲哚]-2,,(1Ή)- The ketone, and the replacement of 2-(bromoindenyl)tetrahydro-2-indole with a (R)-(tetrahydrofuran-2-yl) decyl 4-methylbenzenesulfonate to obtain l'-[(2R)- Tetrahydrofuran-2-ylindenyl]-6,7-dihydro-5Η-spiro[吱,[3,2-g]decene-3,3'-吲哚]-2·(ΓΗ) - Stuffed (57%), as an off-white solid: m.p.: 151 - 156 ° C (diethyl ether); 1H NMR (300 MHz, CDC13) (diastereomers) δ 7.32-7.26 (m,1H), 7.16- 7.02 (m,3H), 6.40 (s,1H), 6.38 (s,1H),4.89 (d, J = 9.0 Hz, 1H), 4.644, 4.640 (d, J = 9.0 Hz, 1H), 4.32-4.24 (m, 1H), 4.11 (dd, J = 5.4, 4.8 Hz, 2H), 3.99-3.69 (m, 4H), 2.63-2.52 (m, 2H), 2.10-1.85 (m, 5H), 1.79-1.67 (m,1H); 13 C NMR (75 MHz, CDC13) (diastereomer) (5 178.3, 178.2, 160.2, 156.3, 143.0, 132.8, 132.7, 128.8, 128.7, 123.88, 123.86, 123.82, 123.76 , 123.3, 121_1, 121.0, 115.2 4, 115.20, 109.7, 109.5,

143924-sp-20091127-3 -473- 201020257 98.9, 80.43, 80.40, 77.1, 77.0, 68.4, 68.3, 66·7, 57.8, 57.7, 44.8, 44.7, 29.4 29.1, 25.8, 25.7, 24.8, 24.7, 22.4; MS (ES+) m/z 378.1 (Μ + 1). Example 4.54 Γ-{[5-(Trifluoromethyl)pyran-2-yl]indolyl 3,4-diargon-2Η-spiro[吱,[2,3-h][l,5] Synthesis of benzodiazepine heptarene-9,3'-吲哚]-2,(1Ή)-_

According to the procedure as described in Example 4, and with irrelevant changes, _ using 3,4-dihydro-2H-spiro[吱,[2,3-h][l,5]benzodioxime七园浠_9,3,_ 嘀哚]-2·(1Ή)-ketone replacement 5,6-dihydrospiro[benzo[1,2-b : 5,4 7']difuran-3,3 ,-巧巧]-2&quot;(1Ή)-ketone' and 2-(bromodecyl)tetrahydro-2Η-peripheryl using 2-(bromodecyl)-5-(trifluoromethyl)pyrene Iso, 1·-{[5-(trifluoromethyl)pyran-2-yl]methyl b 3,4-dihydro-2Η-spiro[吱,[2,3-h][l, 5] benzodioxine heptaene _9,3,_ 啕哚]-2'(1Ή)-one (97%) as a colorless solid: mp 162-164X: (water/methanol); 1H NMR ( 300 MHz, CDC13) ά 7.30 (ddd, J = 7.8, 7.8, 1.2 Hz, 1H), 7.18 (d, J = 7.5 Hz, 1H), 7.07 (dd, J = 7.5, 7.5 Hz, 1H), 6.98 ( d, J = 7.8 Hz, 1H), 6.76-6.73 (m, 1H), 6.60 (s, 1H), 6.39 (d, J = 3.3 Hz, 1H), 6.32 (s, 1H), 5.07 (d, J = 16.4 Hz, 1H), 4.94 (d, J = 9.0 Hz, 1H), 4.89 (d, J = 16.4 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.29-4.21 (m, 1H) ), 4.14-4.02 (m, 2H), 3.99-3.91 (m, 1H), 2.23-2.00 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.1, 156.8, 153.2, 152.1 (q, J = 1.3 Hz), 146.4, 141.8 (q, J = 42.9 Hz), 141.4, 132.1, 129.1, 124.2, 124.0, 122.9, 118.9 (q, J = 267 Hz), 116.1, 112.8 (q, J = 2.7 Hz), 109.4, 109.0, 103.6, 80.4, 70.91, 70.90, 58.0, 37.1, 32.3; MS (ES+) m/z 457.9 (M + 143924-sp-20091127-3 -474 - (8) 201020257 i). Example 4.55 Γ-(tetra)pyridin-2-ylmethyl)-3,4-dihydro-2H_ snail [吱 并 ^ 七 七 七 苯 二 二 -9 -9 -9 -9 -9 -9 -9 -9 , (ΓΗ)-_ synthesis

According to the procedure as described in Example 4, and the insignificant changes were made, 33,4_dihydro-2Η-spiro[吱,[2,3_h][l,5]benzodiazepine seven gardens were used. Alkene-9,3,-W嗓]-2'(1Ή)-嗣substituted 5,6-dihydrospiro[benzo[u_b : 5,4-7,]difuran_3,3W| 嗓]-2" (1Ή)-ketone' and 2-(bromomethyl)tetrahydro-2-indole-peryl using 2-(bromomethyl)pyridine hydrobromide to obtain ι,·(Ρ比啶_2·基曱Base)_3,4_dihydro-2Η-spiro [bito-and-[2,3-h][l,5]benzodiazepine-deceneene_9,3'-吲哚]-2, (1Ή )-ketone (90%), as a colorless solid: m.p. s.: s.sup.sssssssssssssssssssssssssssssssssssssssssssss J = 7.8, 7.5, 1.2 Hz, 1H), ❿ 7.31-7.15 (m, 4H), 7.03 (dd, J = 7.5, 7.5 Hz, 1H), 6.92 (d, J = 7.8 Hz, 1H), 6.61 ( s, 1H), 6.42 (s, 1H), 5.24 (d, J = 15.9 Hz, 1H), 5.04 (d, J = 15.9 Hz, 1H), 4.98 (d, J = 9.0 Hz, 1H), 4.71 ( d, J = 9.0 Hz, 1H), 4.28-4.20 (m, 1H), 4.14-4.05 (m, 2H), 4.02-3.94 (m, 1H), 2.22-2.02 (m, 2H) ; 13 C NMR ( 75 MHz, CDC13) δ 177.5, 156.8, 155.4, 153.1, 149.1, 146.3, 14 2.1, 137.7, 132.2, 129.0, 124.0, 123.7, 123.1, 123.0, 121.9, 116.2, 109.6, 103.6, 80.5, 70.87, 70.85, 58.1, 45.9, 32.2 ; MS (ES+) m/z 401.0 (M + 1) 〇 Example 4.56 2-mercapto-1·-(3-mercaptobutyl)spiro[啥,[2,3-f][l,3]benzothiazole-7,3·-bow 143924-SD- 20091127-3 -475· 201020257 Noise]-2, (1,Η)-ketone synthesis

&gt;-CH3 H3^CH3 Follow the procedure described in Example 4 Φ ήΐ·, +, j* + and perform irrelevant changes, using 2_methyl snail [啥°南和[2,3-f] [l,3] benzoside ° sit -7,3·- ten]-2'(1Ή)-ketone replacement 5,6-monohydrospiro [benzo[12-7:5 4,7]difuran- 3,3,(9)哚]_2,,(1,印_嗣, and using 1-bromo-3-indenylbutane to replace 2_(bromodecyl)tetrahydro-2H_ shout, obtain 2-A Γ-Γ-(3-mercaptobutyl) snail [吱,[2,3 f][1,3]benzopyrazole_7,3,吲嗓]-2'(1Ή)-_ ( 71%), as a colorless solid: mp 137 </ s </ s </ s </ s> hexanes (hexane/ethyl acetate); 1H NMR (300 MHz, CDC13) 5 7.60 (d, J = 8.6 Hz, 1H), 7.32-7.27 (m, 1H) , 7.13-7.08 (m, 1H), 7.03-6.92 (m, 3H), 5.03 (d, J = 8.8 Hz, 1H), 4.78 (d, J = 8.8 Hz, 1H), 4.12-4.01 (m, 1H ), 3.71-3.60 (m, 1H), 2.56 (s, 3H), 1.93-1.61 (m, 3H), 1.06-1.00 (m, 6H) ; 13C NMR (75 MHz, CDC13) δ 176.8, 169.3, 160.4 , 149.4, 142.8, 132.9, 129.1, 128.7, 123.6, 122.8, 122.2, 120.4, 108.6, 108.4, 81.1, 58.2, 39.2, 36.1, 26.0, 23.0, 22.5, 20.3 ; MS (ES+) m/z 378.5 (M + 1). Real 4.57 2-Methyl-indole-(tetrahydro-2H-'pyran-4-ylindenyl) snail [p-dea-[2,3-j〇[l,3]benzopyrazole-7,3 Synthesis of '-哚哚]-2'(1Ή)-_

143924-SP-20091127-3 •476· 201020257 Follow the procedure as described in Example 4, and perform irrelevant changes, using 2-meryl snail [吱,[2,3-f][l,3] Benzoxazole-7,3,-吲哚]-2,(1Ή)-one replaces 5,6-dihydrospiro[benzo[ι,2:5,5,7']difuran_3,3 , _吲哚]-2&quot;(1Ή)-ketone, and using 4-(bromomethyl)tetrahydropyrene to replace 2_(bromomethyl)tetrahydro-2Η ιτ辰喃' to obtain 2-methyl- 1·-(tetrahydro-2Η-piperidin-4-ylmethyl)spiro[吱,[2,3-f][l,3]benzophenanthrene]Km)-one (44%) , as colorless solid: mp 186-187 ° C (hexane / ethyl acetate); iH NMR (300 MHz, CDCl3) δ 7 66_7 6 〇 (m, 1H), 7.34-7.27 (m, 1H), 7.13- 7.07 (m, 1H), 7.06-6.91 (m, 3H), 5.04-4.97 (m, ® 1H), 4.78-4.72 (m, 1H), 4.07-3.93 (m, 3H), 3.52-3.35 (m, 3H), 2.52 (s, 3H), 2.32-2.15 (m, 1H), 2.07-1.95 (m, 1H), 1.91-1.80 (m, 1H), 1.57-1.42 (m, 2H) ; 13C NMR (75 M,,,,,,,,,,,,,,,,,,,,,,,,, ·2 14,6; MS (ES +) m / z 407.0 (M + l). Example 4.58 2-Mercapto-14(2R)-tetrahydrofuran-2-ylmethyl] snail [Homoanthine; benzoxazole-7,3'-吲哚]-2, (1Ή)- Ketone synthesis

.0 according to the procedure as described in Example 4, and with irrelevant changes, use 2_mercaptospiro [furo[2,3-f][l,3]benzoxazole-7,3,-吲哚]-2,(1Ή)-keto-substituted 5,6-dihydrospiro[benzopyrene-7:5,4heptanfuran_3,3,_ρ?丨哚]_2&quot;(1Ή)_one, and Replacement of 2(bromomethyl)tetrahydro-2-indole with a 4-methylbenzenesulfonic acid (8)-tetrahydrofuran-2-yl)methyl ester to give 2-methyl][(2R)-tetrahydrofuran-2-yl Methyl] snail 143924-sp-20091127-3 -477- 201020257 [furo[2,3-f][l,3]benzoxazole-7,3'-吲哚]-2'(1Ή)- Ketone (52%) as colorless solid: mp 188-190°C (ethyl acetate); 1HNMR (300MHz, CDC13) 5 7.37-7.30 (m, 2H), 7.23-7.05 (m, 2H), 6.98-6.93 (m, 2H), 6.00-5.93 (m, 1H), 5.43-5.38 (m, 1H), 4.42-4.26 (m, 1H), 4.05-3.75 (m, 4H), 2.35-2.33 (m, 3H) 2.09-1.79 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 175.6, 175.3, 164.4, 164.3, 151.2, 151.1, 146.2, 146.1, 144.9, 144.6, 138.7, 138.6, 130.5, 130.4, 129.6, 124.6, 124.4, 123.0 (2C), 114.0, 113.9, 111.8, 111.6, 110.6, 110.5, 110.3, 109.8, 88.7, 88.4, 76.1, 76.0 , 68.5, 68.3, 44.7, 44.4, 29.8, 28.9, 26.2, 25.7, 14.7, 14.6; MS (ES+) m/z 414.9 (M + 39). Example 4.59 1-Mercapto-l'-[(2R)-tetrahydrofuran-2-ylindenyl]-1Η-spiro [Miso-[3,2-g][l,4]benzoindole-8, Synthesis of 3'-吲哚]-2,2·(1Ή,3Η)-dione

According to the procedure as described in Example 4, and with irrelevant changes, 1-methyl-1 snail [furo[3,2-lu][1,4]benzoindole-8,3, -啕哚]-2,2·(1Ή,3Η)-dione replacement 5,6-dihydrospiro[benzo[1,2-7:5,4-b,]difuran-3,3,-啕哚]-2&quot;(1Ή)-ketone' and replacing 2-(bromoindenyl)tetrahydro-2-indole-permeate with (R)-(tetrahydrofuran-2-yl)methyl 4-methylbenzenesulfonate, Obtaining 1-methyl-r-[(2R)_tetrahydrofuran-2-ylindenyl]-1Η-spiro [bito-and-[3,2-g][l,4]benzoindole-8,3' -啕哚]-2,2'(1Ή,3Η)-dione (69%) as an off-white solid: m.p.: 79-81°C (diethyl ether); 1H NMR (300 MHz, CDC13) ¢5 7.33 (dd, J = 7.8, 7.8 Hz, 1H), 7.16-7.04 (m, 3H), 6.63-6.62 (m, 1H), 6.39-6.32 (m, 1H), 4.96-4.92 (m, 1H), 4.72-4.67 ( m, 143924-sp-20091127-3 -478- 201020257 1H), 4.54 (s, 2H), 4.37-4.26 (m, 1H), 3.98-3.85 (m, 2H), 3.82- 3.70 (m, 2H), 3.15 (s, 3H), 2.13-2.00 (m, 1H), 1.98-1.88 (m, 2H), 1.78-1.65 (m, 1H); 13C NMR (75 MHz, CDC13) 6 177.7 (2C), 163.9 ( 2C), 157.4, 157.3, 146.9 (2C), 143.1, 142.6, 132.2, 131.9, 12 9.2, 129.1, 124.4 (2C), 123.8 (2C), 123.5, 123.1, 122.8, 109.8, 109.7, 109.6, 100.1 (2C), 80.8, 80.6, 76.9, 76.2, 68.4, 68.2, 67.7, 58.1 (2C), 44.9, 44.6, 29.3, 29.1, 28.5, 28.4, 25.7 (2C) ; MS (ES+) m/z 429.1 (M + 23), 407.1 (M + 1) 〇 Example 4.60 ® 1-Methyl-r-[( 2R)-tetrahydrofuran-2-ylmethyl]spiro[吱,[3,2-f][l,3]benzoindole

Synthesis of azole-7,3'-吲哚]-2,2'(1Η,1Ή)-dione 〇&gt;=〇ΝCH3 Follow the procedure as described in Example 4, and perform irrelevant changes, use 1-曱-based snail [吱,[3,2-f][l,3]benzoxazole-7,3·-吲哚]-2,2Χ1Η,1Ή)-dione replacement 5,6-di Hydrogen snail [benzo[l,2-b: 5,47']difuran-3,3'-&lt; 哚]-2"(1Ή)-® ketone, and 4-mercaptobenzenesulfonic acid ( Replacement of 2-(bromomethyl)tetrahydro-2H-pyran with R)-(tetrahydrofuran-2-yl)methyl ester to give 1-methyl-l'-[(2R)-tetrahydrofuran-2-ylmethyl Snail [吱,[3,2-f][l,3]benzoxazole-7,3'-峋哚]-2,2'(1Η,1Ή)-dione (32%), Colorless solid: melting point &gt; 250 ° C (toluene / hexane); ^ NMR (300 MHz, CDC13) δ 7.38-7.29 (m, 1H), 7.17-7.03 (m, 3H), 6.90-6.85 (m, 1H ), 6.40- 6.28 (m, 1H), 4.99-4.92 (m, 1H), 4.75-4.67 (m, 1H), 4.36-4.25 (m, 1H), 4.01-3.67 (m, 4H), 3.25-3.21 (m, 3H), 2.14-1.85 (m, 3H), 1.79-1.65 (m, 1H); 13 C NMR (75 MHz, CDC13) δ ΠΊ.6, 157.0, 156.9, 155.0, 143.5 (2C),

143924-sp-20091127-3 -479- 201020257 143.1, 142.6, 132.2, 131_9, 129.3, 129.2, 126.2, 124.1, 123.8, 123.6, 109.8, 109.8, 103.1, 103.0, 94.7 (2C), 80.5, 80.4, 77.1, 76.3, 68.4, 68.2, 58.2 (2C), 45.0, 44.7, 29.3, 29.2, 28.3, 28.2, 25.7; MS (ES+) m/z 393.0 (Μ + 1). Example 4.61 6-Methoxy-5-methyl-r-[(2R)-tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran

According to the procedure as described in Example 4, and with irrelevant changes, 6-methoxy-5-mercaptospiro[1-benzofuran_3,3,_啕哚]-2, (1Ή) was used. - Ketone replacement of 5,6-dihydrospiro[benzo[1,2-7:5,4-7']difuran-3,3'-,5丨哚]-2&quot;(1Ή)-one, and use 4 -Methylbenzenesulfonic acid (R)-(tetrahydrofuran-2-yl)methyl ester is substituted for 2-(bromomethyl)tetrahydro-2-indole-pyran' to obtain 6-methoxy-5-methyl-l'- [(2R)-Tetrahydrofuran-2-ylindenyl] spiro[1-benzofuran-3,3·-吲哚]-2'(1Ή)-鲷(72%), as colorless solid: mp 151-153 〇C ; 1H NMR (300 MHz, CDC13) δ 7.27 (dd, J = 7.7, 7.7 Hz, 1H), 7.15-6.98 (m, 3H), 6.48 (s, 1H), 6.44 (s, 1H), 4.90 (d, J = 8.9 Hz, 1H), 4.65 (dd, J = 8.9, 2.3 Hz, 1H), 4.32-4.21 (m, 1H), 3.99-3.61 (m, 4H), 3.78 (s, 3H), 2.10-1.63 (m, 4H), 1.99 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 178.3 (2), 160.3, 159.1, 142.9 (2), 132.6 (2), 128.7 (2), 124.2 ( 2), 123.7 (2), 119.5 (2), 119.2 (2), 109.5 (2), 93.7, 80.4 (2), 77.0 (2), 68.2 (2), 57.9, 55.5, 44.6 (2), 29.1 (2 ), 25.6 (2), 15.9 (2) ; MS (ES+) m /z 366·3 (Μ + 1). Example 4.62 6-Methoxy-5-methyl-indole-(pyridin-2-ylindenyl)spiro[1-benzofuran-3,3·-Μ丨143924-sp-20091127-3 -480· 201020257哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 4, and with irrelevant changes, 6-methoxy-5-methylspiro[ι_笨和furan_3,3,_ρ?丨哚]_2, (1Ή) was used. -ketones to replace 5,6-dihydrospiro[benzo[i,2-b:5,4-7,]difuran-3,3,-chico]-2"(1Ή)-one, and 2- (Bromo fluorenyl acridinium hydrobromide replacement 2_(bromomethyl)tetra argon _211_pipetaxo 1' to obtain 6-decyloxy-5-methyl-indole-(pyridin-2-yl-methyl) Spiral [1-benzofuran-3,3'-indole]-2'(1Ή)-one (82%) as colorless solid: m.p. 2-1441; WNMR (300 MHz, CDC13) δ 8.56 (d, J = 4.8 Hz, 1H), 7.67-7.60 (m, 1H), 7.28-7.11 (m, 4H), 7.00 (dd, J = 7.5, 7.5 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 6.50 (s, 2H), 5.09 (ABq, 2H), 4.84 (ABq, 2H), 3.79 (s, 3H), 2.00 (s, 3H) ; 13 C NMR (75 MHz, CDCI3) δ 178.0, 160.3, 159.2, 155.7, 149.5, 142.5, 142.2, 137.1, 132.6, 128.7, 124.3, 123.8, 123.5, 122.8, 121.7, 119.5, 119.2, 109.5, 93.8, ❷ 80.3, 58.0, 46.1, 22.6, 16.0; MS (ES+) m/z 373.3 (Μ + 1). Example 4.63 6-Methoxy-5-methyl-indole-(tetrahydro-2H-pyran-2-ylmethyl)spiro[1-benzene Squeak thiopyran-3,3, - indol] -2 · (1Ή) - one Synthesis of

According to the procedure as described in Example 4, and with irrelevant changes, 6-decyloxy-5-methylspiro[1-benzofuran-3,3W丨哚]-2·(1·Η) was used. -嗣 replacement 143924-SD-20091127-3 -481 - 201020257 5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-吲哚]- 2&quot;(1Ή)-ketone, 6-decyloxy-5-mercapto-indole-(tetrahydro-2-indole-pyran-2-ylmethyl)spiro[1-benzofuran-3,3'-啕哚]-2'(1Ή)-one (68%) as a colorless solid: mp. 180-182. (: ; iHNMR (300 MHz, CDC13) (5 7.28 (dd, J = 7.8, 7.8 Hz, 1H), 7.13-6.97 (m, 3H), 6.47 (s, 1H), 6.43 (d, J = 4.3 Hz , 1H), 4.91 (dd, J = 8.9, 2.1 Hz, 1H), 4.66 (dd, J = 8.9, 3.3 Hz, 1H), 4.02-3.59 (m, 4H), 3.79 (s, 3H), 3.43- 3.31 (m, 1H), 1.99 (s, 3H), 1.92-1.77 (m, 1H), 1.71-1.26 (m, 5H); MS (ES+) m/z 380.4 (M + 1). Example 4.64 5- Fluoro-6-methoxy-indole-(tetrahydro-2H-&gt;pyran-2-ylmethyl)spiro[1-benzofuran-3,3,爿|哚]-2'(1' 11) - Synthesis of ketone

5-fluoro-6-methoxyspiro[1-benzofuran-3,3'-oxime]-2' (1 Ή) was used according to the procedure as described in Example 4, and irrelevant changes were applied. -_Substituting 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2"(1Ή)-one to obtain 5- Fluoro-6-methoxy-indole-(tetrahydro-2Η-piperidin-2-ylindenyl)spiro[1-benzofuran-3,3·-吲嗓]-2'(1Ή)-one (99%) as colorless solid: m.p. 131- 133°C; 1H NMR (300 MHz, CDCI3) δ 7.31-7.24 (m, 1 Η), 7.13-6.98 (m, 3H), 6.61-6.55 (m, 1H ), 6.47-6.39 (m, 1H), 4.96-4.89 (m, 1H), 4.71-4.63 (m, 1H), 4.00-3.76 (m, 5H), 3.73-3.59 (m, 2H), 3.42-3.30 (m, 1H), 1.91-1.79 (m, 1H), 1.70-1.27 (m, 5H); 13CNMR (75MHz, CDC13) δ 177.5, 177.4, 157.10, 157.08, 157.05, 157.03, 149.2, 149.0, 148.8, 146.1 , 143.2, 143.0, 131.9, 131.8, 128.9, 128.8, 143924-SO-20091127-3 •482· 201020257 123.52, 123.50, 123.18, 123.15, 119.4, 119.3, 119.2, 110.6, 110.5, 110,3, 110.2, 109.9, 109.8, 96.2, 80.4, 75.6, 75.4, 68.4, 68.3, 57.96, 57.95, 57.92, 56.4, 45.7, 45.6, 29.5, 29.4, 25.7, 23.0; MS (ES+) m/z 384.2 (Μ + 1). Example 4.65 5-Fluoro-6-methoxy-l'-opyridin-2-ylmethyl)spiro[1-benzofuran_3,3 ·-啕哚]-2'(1Ή)-ketone synthesis

9 Using a procedure as described in Example 4, and applying an insignificant change, 5-fluoro-6-methoxyspiro[1-benzofuran-3,3'-呻哚]-2, (1Ή) a ketone to replace 5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-啕哚]-2··(1Ή)-one, and 5-(Chloromethyl)tetrahydro-2-indole-periep-[2-(bromomethyl)tetrahydro-2-indole-p-[upsilon] was obtained using 2-(bromo-mercaptohydropterylide hydrobromide) to give 5-fluoro-6-methoxy-indole-(pyridine-2- (N-benzofuran-3,3'-indole]-2'(1Ή)-one (77%) as colorless solid: mp 142-144t; WNMR (300 MHz, CDC13) δ 8.59-8.53 (m, 1Η), 7.65 (ddd, J =: 7.7,7.7, 1.7 Hz, 1H), ❹ 7.28-7.10 (m, 4H), 7.01 (dd, J = 7.5, 7.5 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.60 (d, J = 6.8 Hz, 1H), 6.52 (d, J = 10.1 Hz, 1H), 5.20 (d, J = 15.8 Hz, 1H), 5.03- 4.90 (m, 2H), 4.72 (d, J = 9.0 Hz, 1H), 3.86 (s, 3H) ; 13C NMR (75 MHz, CDCI3) δ 177.3, 157.2 (d), 155.4, 149.6, 149.3, 149.1, 149.0, 146.1, 142.1, 137.1, 131.8, 129.0, 123.8, 123.6, 122.8, 121.6, 119.0 (d), 110.7, 110.4, 109.6, 96.3, 80.5, 58.1, 56.4, 46.0; MS (ES+) m/z 377.2 ( M + 1). Example 4.66 5-Fluoro-6-methoxy-1'-[(2R)-iz9hydrofuran-2-ylindenyl]spiro[1-benzofuran 143924-SP-20091127-3 -483-201020257 - Synthesis of 3,3,5i哚]-2丨(1Ή)-ketone

〇, ch3 According to the procedure as described in Example 4, and the insignificant change was made, 5-fluoro-6-methoxyspiroU_benzofuran_3,3,_吲哚]_2, (1Ή) was used. The ketone replaces 5,6-dihydrospiro[benzo[i,2-b:5,47']difurazan-3,3W丨哚]-2"(1Ή)-_, and uses 4- (r)-(tetrahydrofuran-2-yl) decyl methacrylate is substituted for 2_(bromodecyl)tetrahydro-2H-methane to give 5-fluoro-6-methoxy-1,-[ (2R)-e3hydrofuran-2-ylmethyl]indole [1-benzopyrene η南_3,3'-p 嗓]_2'(1Ή)-_ (42%), as a colorless solid: , melting point 106-116 〇C; 1H NMR (300 MHz, CDC13) δ 7.28 (dd, J = 7.6, 7.6 Hz, 1H), 7.14-6.98 (m, 3H), 6.58 (d, J = 6.8 Hz, 1H), 6.49-6.40 (m, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.31-4.19 (m, 1H), 3.98-3.64 (m , 7H), 2.09-1.80 (m, 3H), 1.76-1.61 (m, 1H) ; 13C NMR (75 MHz, CDC13) δ 177.7, 177.5, 157.1, 149.3, 149.1, 148.9, 146.1, 142.8, 131.9, 131.7 , 129.0, 128.9, 123.7, 123.6, 123.3, 119.3' 119.2, 110.6, 110.5, 110.3, 110.2, 109.8, 109.6, 96.3, 80.6, 76.7, 68.2, 68.1, 58.0, 56.4, 44.6, 29.2, 29.0, 25.7, 25.5 ; MS (ES+) m/z 370.2 (M + 1) ° Example 4.67 Γ-爷基-5-fluoro-6-methoxyspiro[1-benzofuran-3,3 ·-啕哚]-2·(1Ή)-ketone synthesis 143924-SP-20091127-3 -484- (S) 201020257

According to the procedure as described in Example 4, and the insignificant change was made, 5-fluoro-6-fluorenyl spiro[i_benzofuran·3,3,_ρ哚哚]_2'(1Ή)_ was used. Ketone replacement of 5,6-hydrogen snail [benzo[i,2-b:5,4,7]difuran-3,3,-&lt; 哚]-2Π(1Ή)-one, and use of benzyl bromide Displacement of 2-(bromohydrazino)tetrahydro-2-indole-pyran to obtain Γ-benzyl _5-fluoroyl φ_6_ fluorenyl spiro[1_benzofuran-3,3,-啕哚]- 2'(1Ή)-ketone (86%) as a colorless solid. m.p. 160-162. (: ; 1H NMR (300 MHz, CDC13) 5 7.39-7.26 (m, 5Η), 7.20 (ddd, J = 7.6, 7.6, 1.2 Hz, 1H), 7.16-7.09 (m, 1H), 7.06-6.97 ( m, 1H), 6.79 (d, J = 7.8 Hz, 1H), 6.61 (d, J = 6.8 Hz, 1H), 6.43 (d, J = 10.1 Hz, 1H), 5.05 (d, J = 15.5 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.83 (d, J = 15.5 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 3.86 (s, 3H); 13 C NMR ( 75 MHz, CDC13) δ 182.3, 173.3, 166.3, 165.6, 147.9, 137.5, 133.7, 128.5, 128.0, 126.1, 124.9, 124.6, 114.2, 97.5, 84.9, 77.3, 62.0, 47.6, 33.5 ; MS (ES+) m/ z 376.0 (M + 1). G Example 4.68 6-decyloxy-14(2R)-tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran-3,3,_啕哚]-2' ( 1Ή)-ketone synthesis

According to the procedure as described in Example 4, and insignificantly changing, 6-methoxyl spiro[1-benzofuran-3,3'-啕哚]-2·(1Ή)-one was substituted 5 ,6-dihydrogen 143924-sp-20091127-3 •485 · 201020257 snail [benzo[l,2-b : 5,4-b']difuran-3,3'-吲哚]-2" (1Ή -ketone, and replacing 2-(bromomethyl)tetrahydro-2-indole-pyran with (R)-(tetrahydrofuran-2-yl)methyl 4-mercaptobenzenesulfonate to give 6-decyloxy- R-[(2R)-rahydrofuran-2-ylmethyl]spiro[1-benzofuran-3,3'-indole]-2·(1Ή)-one (54%) as a colorless liquid: 4 NMR (300 MHz, CDC13) (diastereomer) (5 7.32-7.25 (m, 1H), 7.16-6.99 (m, 3H), 6.61 (d, J = 8.1 Hz, 1H), 6.52 ( d, J = 2.1 Hz, 1H), 6.36 (dd, J = 8.1, 2.1 Hz, 1H), 4.94 (d, J = 9.0 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.32- 4.22 (m, 1H), 4.00-3.66 (m, 4H), 3.77 (s, 3H), 2.10-1.66 (m, 4H); 13C NMR (75 MHz, CDC13) (diastereomer) 5 178.0 , 177.9, 162.0, 161.4, 142.9, 142.8, β 132.4, 132.3, 128.7, 128.6, 123.6, 123.5 (2C), 123.4, 123.2, 121.0, 120.9, 109.6, 109.3, 107.4 (2C), 96.5, 80.5, 80.4, 76 .8, 76.7, 68.2, 68.1, 57.5, 55.5, 44.5 (2C), 29.2, 28.9, 25.6, 25·5; MS (ES+) m/z 352.1 (Μ + 1). Example 4.69 6-Bromo-l Synthesis of '-[(2R)-rahydrofuran-2-ylmethyl]spiro[l-benzofuran_3,3,_P丨哚丨哚]-2'(1Ή)-one

. in 6-bromospiro[1-benzofuran_3,3W丨哚]_2, (1'Η), (1 3 g, 4 3 mmol) in 2-butanone (40.0 mL) In the stirred solution, add carbonic acid planing (4 2 g ' 12.9 mmol) and 4-methylbenzoic acid (R)-(tetrahydrofuran-2-yl) decyl ester q 4 g ' 5.4 mmol ear). The reaction was refluxed for 16 h, filtered and concentrated in vacuo to dry. The residue was purified by flash chromatography using 25% ethyl acetate in hexanes to give 6-bromos, s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s -486· 201020257 Benzoin-3,3,- 哚 哚]-2,(1,H)-one (1.75 g, 100%), as colorless solid: MS (ES+) m/z 400.0 (M + 1), 402.0 (M + 1). Example 4.70 1'-{[5-(Trifluoromethyl)pyran-2-yl]indenyl}_2,3,6,7_tetrahydrospiro[N,2_Asterene-5 ,3'-啕哚]-2'(1Ή)-_ synthesis

According to the procedure as described in Example 4, and with irrelevant changes, 2,3,6,7-tetrahydrospiro[吱,[3,2-g]p gram-5,3,-θ was used. Budu]-2'(1,Η)-阙 substitution 5,6-dihydrospiro[benzo[1,2:7:5,4-1)']difuran-3,3,-啕哚]- 2,, (1Ή)-ketone, replacing acetone with butanone and 2-(bromomethyl)-5-(trifluoromethyl)furan for 2-(exylmethyl)tetrahydro-2-indole , Γ-{[5·(Trifluoromethyl)pyran-2-yl]methyl}-2,3,6,7-tetrahydrospiro[3,2-g]decene ·5,3,_吲哚]-2'(1Ή)-ketooxime (43%) as a colorless solid: 1H NMR (300 MHz, CDC13) (5 7.36-6.93 (m, 4 Η), 6.76-6.70 ( m, 1H), 6.38 (d, J = 3.5 Hz, 1H), 6.36 (s, 1H), 6.21 (s, 1H), 4.98 (ABq, 2H), 4.80-4.69 (m, 1H), 4.45 (t , J = 8.6 Hz, 2H), 4.36-4.28 (m, 1H), 2.92 (t, J = 8.5 Hz, 2H), 2.23-2.16 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 179.3 , 160.6, 155.5, 152.2, 152.1, 141.8, 141.6, 141.3, 135.2, 128.3, 124.1, 123.5, 123.5, 120.6, 120.4, 117.0, 112.6 (2C), 112.5 (2C), 112.1, 109.1, 108.6, 98.6, 71.8 , 62.0, 47.8, 36.7, 32.4, 28, 8 ; MS (ES+) m/z 441.7 (M + 1). Example 4.71 methylthio)-yl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]dioxan-3, 3'-啕143924-sp-20091127-3 -487- 201020257 p-wood]-2'(l'H)-ig synthesis

According to the procedure as described in Example 4.22, and irrelevant changes were made, (4-(&gt; odorylmethyl) benzyl) (fluorenyl) sulphur was used to replace 漠-m-toluene carbonitrile to obtain hydrazine- [4-(indolyl)-yl]-5,6-dihydrospiro[benzo[u_b:5 4_b,]difuran-3,3'-oleole]-2'(1Ή)-嗣(61 %) ' is a colorless solid: MS (ES+)(10): 416 2 (M Example 4.72 l'-{[(2S)-5-ketotetrahydropyrrole-2-yl]methyl} snail [pyranobenzene Synthesis of dioxynene-7,3'-吲哚]-2,(1'Η)-one

According to the procedure as described in Example 4, and irrelevant changes were made, (R)-3-bromomercapto-2-tetrahydropyrrolone was substituted for 2_(bromoindenyl)tetrahydro-2-indole, And replacing the 5,6-dihydrospiro[benzene] with a snail [吱,[2,3-f][l,3]benzodioxanthene-7,3,-峋哚]-2Χ1Ή)-one And [i,2-b: 5,4-b,]difuran-3,3,-蚓哚]-2"(1Ή)-ketone' obtains r-{[(2S)-5-ketotetrahydro Pyrrol-2-yl]methyl} snail [snuryl arsenic [2,3-phan [1,3] benzodioxolan]-7,3'-蚓哚]-2'(1'11)- Ketone (47%) as a colorless solid: m.p. 121-130°C; iHNMROOOMHLCDsOD)^?%^,]:?.^ 7.6 Hz, 1H), 7.22-7.06 (m, 4H), 6.48 (d, J = 1.9 Hz, 1H), 6.15 (d, J = 9.3 Hz, 143924-sp-20091127-3 -488- 201020257 1H), 5.82 (d, J = 1.4 Hz, 2H), 4.86-4.81 (m, 2H), 4.64 (dd, J = 9.3, 3.8 Hz, 1H), 4.13-4.06 (m, 1H), 3.85-3.83 (m, 2H), 2.43-2.18 (m, 2H), 2.00-1.88 (m, 1H); 13C NMR (75 MHz, CD3OD) δ 111.9, 177.4, 177.3, 154.7, 154.6, 147.5, 147.4, 141.2, 140.8' 140.8, 136.0, 130.8, 130.6, 127.3, 127.2, 127.0, 126.3, 123.4, 122.0, 121.9, 121.9 , 1 18.0, 117.8, 107.4, 101.1, 100.0, 99.9, 91.3, 91.3, 78.8, 78.7, 56.8 (2C), 51.4, 51.2, 43.2 (2C), 27.6, 22.6, 18.6 ; MS (ES+) m/z 401.2 (M + 23), 379.2 (M + 1). Example 4.73 ® (2'-oxyspiro[,,[2,3-f][l,3]benzodioxene-7,3·-啕哚]-Γ(2Ή)-based) Synthesis of acetonitrile

Following the procedure as described in Example 4, and carrying out irrelevant changes, the replacement of 2-(bromomethyl)tetrahydro-2-indole with chloroacetonitrile and the use of spiro[2,3-f ][l,3]benzodioxanthene-7,3'-啕哚]-2'(1Ή)-one substituted 5,6-dihydro® spiro[benzo[l,2-b: 5 , 4-b,]dinan-3,3,-θ1 嗓]-2&quot;(1Ή)-ketone, obtained (2,-oxo[furo[2,3-f][l,3]benzo Dioxolene-7,3,-啕哚]-1,(2Ή)-yl)acetonitrile (61%) ' is a colorless solid: m.p. ) δ 7.38 (dt, J = 1.1 y 1.2 Hz, 1H), 7.26 (d, J = 7.7 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 7.11 (dt, J = 7.7, 1.1 Hz) , 1H), 6.66 (s, 1H), 6.21 (s, 1H), 5.89 (d, J = 1.5 Hz, 2H), 4.94 (ABq, J = 17.9 Hz, 2H), 4.73 (ABq, J = 9.5 Hz , 2H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.8, 155.8, 148.9, 142.232, 141.0, 131.9, 129.4, 124.3, 124.3, 119.8, 116.0, 109.7, 103.5, 101.9, 93.8, 143924-sp-20091127 -3 -489- 201020257 80.1, 57.8,28.8 , MS (ES+) m/z 321.3 (M + 1) 〇Example 4.74 7·-(Triplemethane)-1'-{[5-(Trifluoromethyl "husband Synthesis of meryl]methyl}spiro[吱,[2,3-f][l,3]benzodioxolene-7,3,吲哚]_2,(1Ή) ketone

Following the procedure as described in Example 4, and carrying out an insignificant change, the 5-bromomethyl-2-(trifluoromethyl)-anthracene was substituted for 2-(bromodecyl)tetrahydro-2-indole. And using 7'-(trifluoromethyl)spiro[[,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, ,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3'-decade]-2Π(1Ή)-one, obtaining 7,-(trifluoromethyl) Trifluoroindolyl)_2_furanylmethyl}spiro[furo[2,3-f][l,3]benzodioxolene-7,3,_啕哚]-2' ( 1Ή)-- (43%) as a colorless solid: m.p. 95-98°C; 1H NMR (300 MHz, CDC13) d 7.59 (d, J = 8.1 Hz, 1H), 7.36 (d, J = 7.3 Hz, 1H), 7.15 (dd, J = 7.8, 7.8 Hz, 1H), 6.69 (d, J = 3.2 Hz, 1H), 6.50 (s, 1H), 6.23 (d, J = 3.0 Hz, 1H), 6.10 ( s, 1H), 5.86 (d, J = 3.0 Hz, 2H), 5.23 (ABq, 2H), 4.78 (ABq, ® 2H) ; 13C NMR (75 MHz, CDC13) δ 178.6, 156.0, 152.2, 149.3, 142.7 , 141.4 (q), 139.1, 135.1, 127.9, 127.0 (m), 122.9 (d), 121.1 (d), 119.3 (d), 118.7.113.4 (q), 112.5, 108.2, 102.8, 101.7, 93.7, 80.8 , 56.9, 39.4 ; MS (ES+) m/z 498.4 (M + 1). Example 4.75 Γ-[(5-Alkyl-2-pyrimenyl)methyl]-7·-(trifluoromethyl) snail [rudo[2,3-f][l,3] stupid and Synthesis of Oxygenene-7,3·-啕哚]-2'(1Ή)-ketone 143924-SP-20091127-3 -490- 201020257

置换 Replace 2-(bromomethyl)tetrahydro-211_piperazin with 2-methyl-5-(carbomethyl)P-cetin according to the procedure described in Example 4 and with irrelevant changes 'and using 7'-(trifluoromethyl)spiro[吱,[2,3-f][l,3]benzodioxanthene oxime]-2·(1Ή)-one substitution 5, 6-Dihydrospiro[benzo[1,2-7:5,4-iy]difuran-3,3W丨嗓]_2"(1Ή)_ketone' obtained Γ_[(5_气基_2_μ" Methyl]_7,_(trifluoromethyl)spiro[吱,[2,3-f][l,3]benzodioxene _7,3'_吲哚]_2, ( 1Ή) ketone (95%) 'as a colorless solid άβ) δ 7.66 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 7.2 Hz, 1H), 7.24 (dd, J = 7.8, 7.8

Hz, 1H), 6.93 (d, J = 3.8 Hz, 1H), 6.80 (d, J = 3.8 Hz, 1H), 6.70 (s, 1H), 6.22 (s, 1H), 5.91 (d, J = 4.4 Hz, 2H), 5.09 (ABq, 2H), 4.78 (ABq, 2H); 13 C NMR (75 MHz, DMSO-d6) δ 178.9, 156.2, 149.2, 142.4, 139.9 (2C), 138.7, 135.4, 129.1, 127.4, 127.2, 126.9, 125.9, 123.9, 119.4, 111.5, 103.5, 102.0, 93.9, 80_7, 56.5, 42.3; MS (ES+) m/z 481.2 (M + 1), 479.9 (M + 1). Example 4.76 Γ-[(2-Isopropyl-1,3-farsin-5-yl)methyl]_7,-(trifluoromethyl)spiro[吱,[2,3-f][l, 3] benzodioxolone _7,3,_吲哚]_21 (1 ketone-ketone synthesis

Following the procedure as described in Example 4, and carrying out an insignificant change, replacing 5-(bromodecyl)tetrahydro-2H_^ 143924 with 5-methylmethyl-2-(isopropyl)u-serazole- Sp-20091127-3 -491 - 201020257 喃, and using 7·-(trifluoromethyl) snail [e-and-[2,3-f][l,3] benzodioxolan-7-3 '-吲哚]-2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[1,2-7:5,4-7]difuran-3,3%5丨嗓]-2" ( 1Ή)-ketone, obtaining Γ-[(2-isopropyl-1,3-oxazol-5-yl)methyl]-7'-(trifluoromethyl) snail [biting and argon [2,3- £][1,3]benzodioxene-7,3·-^ 哚]-2ΌΉ)-one (51%), as a colorless solid: m.p. 〇3°C; 1HNMR (300 MHz , DMSO-d6) δ 7.61 (d, J = 8.1 Hz, 1H), 7.48 (d, J = 6.8 Hz, 1H), 7.23 (dd, J = 7.8, 7.8 Hz, 1H), 7.18 (s, 1H) , 6.69 (s, 1H), 6.48 (s, 1H), 5.91 (s, 2H), 5.08 (ABq, 2H), 4.77 (ABq, 2H), 3.21-3.16 (m, 1H), 1.22 (d, J = 6.9 Hz, 6H); 13 C NMR (75 MHz, DMSO-d6) &lt;5 178.7, 177.4, 156.0, 150.7, 149.0, 142.3, 140.7, 135.6, 128.7, 125.7, 124.5 (6), 123.6, 119.8, 113.3, 111.5 (m), 103.9, 101.9, 93.8, 8 0.8, 56.6, 43.3, 32.8, 23.3; MS (ES+) m/z 489.4 (M + 1) Example 4.77 l'-[(2-Isopropyl-1,3"oxazol-5-yl)indenyl] Synthesis of snail [吱,[2,3-f][l,3]benzodioxol-7,3,-吲哚]-2,(1Ή)-one

Following the procedure as described in Example 4, and carrying out irrelevant changes, replacing 2-(bromomethyl)tetrahydro-2-indole with 5-methylmethyl-2-isopropylcarbazole, and using snails Bufmano[2,3-fKU]benzodioxanthene_7,3,_吲哚]_ 2'(1Ή)-one substituted 5,6-dihydrospiro[benzo[u_b : 5 , 4,7,]difuran_3 3,吲哚]_ 2 (1 H)-one, obtaining 1'-[(2-isopropylcarbazol-5-yl)methyl] sulphate 2,3-f][l,3]benzodioxanthene_7 3W丨哚]_2,(1Ή)ketone (11%), colorless solid 143924-sp-20091127-3 -492- 201020257 : melting point 75-77 ° C; 1H NMR (300 MHz, CDC13) (5 7.42 (s, 1H), 7.26 (dd, J = 7.4, 7.4 Hz, 1H), 7.15 (d, J = 7.3 Hz, 1H) , 7.07-7.00 (m, 2H), 6.48 (s, 1H), 6.15 (s, 1H), 5.83 (d, J = 4.2 Hz, 2H), 4.83 (ABq, 2H), 4.78 (ABq, 2H), 3.10-2.95 (m, 1H), 1.30 (d, J = 7.0 Hz, 6H); 1 3C NMR (75 MHz, DMSO-d6) δ 1773,169.4, 155.8, 148.9, 142.3, 141.8, 135.3, 135.1, 132.2 , 128.9, 123.8, 123.5, 119.5, 109.6, 103.1, 101.5, 93.6, 80.3, 58.2, 36.6, 28.5, 20.4, 20.3; MS (ES+) m/z 405.4 (M + 1) ° Example 4.78

[1-cyclopropyl-3-(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxauthene-7,3'-吲哚]-Γ( Synthesis of 2Ή)-yl)propyl]aminocarbamic acid tert-butyl ester

Displacement of 2-(bromodecyl)tetrazide with amino-tert-butyl-3-bromodecyl-1-cyclopropyl amino phthalate according to the procedure described in Example 4 and subject to insignificant changes Hydrogen-2Η-pyranose' and the use of spiro[吱,[2,3-f][l,3]benzodioxosyl-7,3·-throindole]-2·(1Ή)-one Substitution of 5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3^0]-2&quot;(1Ή)-ketone' to obtain [μcyclopropyl _3_(2,_Oxospiro[吱,[2,3-f][l,3]benzodioxolene-7,3,_吲哚]4,(2Ή)_yl)propyl Aminobutyric acid tert-butyl ester (91%) 'is a fluffy yellow solid: iH nmr (3〇〇μηζ, CDC13) δ 7.28 (dd, J = 7.7, 7.7 Hz, 1H), 7.13 (d, J = 6.9 Hz, 1H), 7.02 (dd, J = 7.2, 7.2 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 6.47 (s, 1H), 6.11 (d, J = 4.9 Hz, 143924-sp-20091127-3 -493- 201020257 1H), 5.83 (d, J = 5.5 Hz, 2H), 4.88 (dd, J = 8.9, 7.0, Hz, 1H), 4.69 (br, 1H), 4.62 ( Dd, J = 8.9, 1.7 Hz, 1H), 3.93-3.73 (m, 2H), 2.99 (br, 1H), 2.14-1.81 (m, 2H), 1.30 (s, 9H), 0.95-0.80 (m, 1H), 0.58-0.19 (m, 4H); 13 C NMR (75 MHz, CDC13) &lt;5 177. 3, 177.3, 155.9, 155.7, 155.6, 148.8, 142.3, 142.2, 132.4,

129.0, 123.9, 123.3, 119.5, 119.4, 108.6, 103.1, 103.0, 101.5, 93.6, 80.4 (2C), 65.9, 58.2, 37.8, 37.5, 32.9, 32.7, 28.4, 16.1 (2C), 15.3, 3.9, 3.8, 3.0, 2.9 ; MS (ES+) m/z 501.3, (M + 23), 479.28 (M + 1), 423.2 (M - 56), 379.3 (M -100) 〇 Example 4.79 l'-[4-(曱Synthesis of thio)benzyl]spiro[吱,[2,3-f][l,3]benzodioxol-7,3'-吲哚]-2'(1Ή)-one

Following the procedure as described in Example 4, and carrying out irrelevant changes, the replacement of 2-(bromomethyl)tetrahydro-2-indole with 4-(methylthio)benzyl bromide, and the use of spiro[ρ Fusino[2,3-f][l,3]benzodioxol-7,3,-W哚]-2,(1Ή)-one substituted 5,6-a snail [benzo [l,2-b : 5,4-b']2,3'-ρ5丨**--2&quot;(1Ή)-ketone, obtain Γ-[4-(methylthio) [Crystal] snail [c-c-[2,3-f][l,3] benzodioxolan-7,3,-W 嗓]-2'(1Ή)-one (86%), Colorless solid: m.p. 128-13 (TC; iHNMR (300 MHz, DMSO-d6) δ 7.28-7.19 (m, 5H), 7.14 (d, J = 7.0 Hz, 1H), 7.00 (d, J =

V.5 Hz, 1H), 6.96 (d, J = 7.8 Hz, 1H), 6.68 (s, 1H), 6.14 (s, 1H), 5.89 (d, J = 1.9 Hz, 2H), 4.87-4.79 ( m, 3H), 4.67 (d, J = 9.3 Hz, 1H), 2.40 (s, 3H) ; 1 3 C 143924-sp-20091127-3 • 494- 201020257 NMR (75 MHz, DMSO-d6) δ 177.3, 155.9, 148.8, 142.6, 142.2, 137.8, 133.3, 132.1, 129.3, 128.4, 126.6, 124.2, 123.6, 120.1, 109.9, 103.3, 101.9, 93.8, 80.4, 57.9, 43.2, 15·1; MS (ES+) m/ z 418.1 (M+l). Example 4.80 3-(2'-oxo[[,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, Synthesis of propionitrile

According to the procedure as described in Preparation 44, and irrelevant changes were made, 3-bromopropionitrile was used to replace α-bromo-m-toluene carbonitrile, and snail [snake[2,3-f][ l,3]benzodioxolene _7,3,_, 哚]_2, (1Ή)-ketone replacement 5,6_dihydrospiro [benzo[l,2-b: 5,4- b] 二吱"South-3,3,-〃引嗓]-2,,(1Ή)-ketone, obtain 3-(2,-oxospiro[吱,[2,3-f][l,3 ] benzodioxanthene _7,3,_吲哚]_Γ(2Ή)-yl)propanenitrile (86%) ' is a colorless solid: melting point 2〇〇_2〇2°c; iH NMR (300 MHz, DMSO-d6) δ 7.32 (ddd, J = 7.6, 7.4, 1.2 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 6.7 Hz, 1H), 7.04 (ddd , J = 7.4, 7.4, 1.0 Hz, 1H), 6.66 (s, 1H), 6.24 (s, 1H), 5.89 (d, J = 2.2 Hz, 2H), 4.69 (ABq, J = 9.3 Hz, 2H) , 4.10-3.88 (m, 2H), 2.95 (t, J = 6.5 Hz, 2H); 13 C NMR (75 MHz, DMSO-d6) δ 177.1, 155.8, 148.8, 142.2, 141.9, 132.3, 129.3, 124.1, 123.7, 120.1, 119.1, 109.8, 103.6, 101.9, 93.7, 80.3, 57_9, 35.9, 16.2; MS (ES+) m/z 335.1 (M + 1). Example 4.81 Γ-[(2-Mosyl-1,3-indolyl-5-yl)methyl] snail [吱 并 阳 - 幻 ie] benzodioxosyl-7,3'-吲哚]_2, (l,H)-keto synthesis 143924-sp-20091127-3 -495- 201020257

Following the procedure as described in Example 4 and performing an insignificant change' using 2-bromo-(5-mentamoylmethyl), the stopper replaced 2_(bromoindenyl)tetrahydro-211. Displacement of 5,6-dihydrospiro with spiro[吱,[2,3-f][l,3]benzodioxene-7,3,-ten]-2'(1Ή)-one [Benzo[i,2-b:5,4-b.]difuran-3,3'-,?丨哚]-2&quot;(1Ή)-ketone' obtained Γ-[(2-bromo-1 , 3-Oxazol-5-yl)methyl] snail [吱,[2,3-f][l,3]benzo-oxo-cetene-7,3'-θbdu]-2' (1Ή)-ketone (94%) as a colorless solid: m.p. 215-217 〇 C; 1H NMR (300 MHz, DMSO-d6) &lt;5 7.81 (s, 1H), 7.34-7.24 (m, 2H), 7.15 (d, J = 7.2 Hz, 1H), 7.03 (ddd, J = 7.3, 7.3, 1.3 Hz, 1H), 6.67 (s, 1H), 6.13 (s, 1H), 5.89 (d, J = 3.9 Hz , 2H), 5.11 (s, 2H), 4.69 (ABq, 2H) ; 13 C NMR (75 MHz, DMSO-d6) ^ 177.0, 155.9, 148.9, 142.9, 142.2, 141.7, 138.2, 136.4, 132.1, 129.4, 124.3, 123.9, 119.9, 109.7, 103.4, 101.9, 93.8, 80.2, 57.8, 36.3; MS (ES+) m/z 458.9 (M + 1), 456.9 (M + 1). Example 4.82 1 ki--4-(dimethyl-methyl ketoxime-5-yl) fluorenyl} snail [bite. Nanhe [2'3-f][l,3] benzodioxolane -7, Synthesis of 3'_吲哚]-2'(1Ή)-ketone

F3c Following the procedure as described in Example 4, and performing an insignificant change, 5-(bromohydrazinyl)-4-(trifluoromethyl)-pyrazole-2-amine was substituted for 2-(bromohydrazine) Base) 143924-sp-20091127-3 -496- 201020257 Hydrogen-2H-pyranose' and the use of spiro[吱,[2,3-f][l,3]benzodioxol-7, 3,-吲哚]-2'(1Ή)-ketone replacement 5,6-dihydrospiro[benzo[i,2-b : 5,4-b']difuran-3,3'-峋嗓] -2''(ΓΗ)-ketone, obtaining Γ-{[2-amino-4-(trifluoromethyl)-1,3-oxazol-5-yl]indenyl} snail [biting and arranging [2] ,3-f][l,3]benzodioxanthene-7,3,-啕哚]-2,(1Ή)-嗣(4.0%), is a colorless solid··melting point i65_167°c; ΐΗΝΜΙΐρΟΟΜΗζ , ϋΙ^Ο-Α) accounted for 7.39 (br, 2Η), 7.32 (dd, J = 7.7, 7.7 Ηζ, 1Η), 7.18 (d, J = 6.7 Ηζ, 1Η), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.98 (d, J = 7.8 Hz, 1H), 6.69 (s, 1H), 6.12 (s, 1H), 5.91 (s, 2H), 5.02 (ABq, 2H), 4.70 (ABq, 2H 13C NMR (75 MHz, ® DMSO-d6) δ 176.8, 167.9, 155.9, 148.9, 142.2, 141.8, 134.7 (q, 1 JCF= 135 Hz), 132.1, 129.5, 124.5, 123.9, 123.8 (m), 119.9, 109. 2, 103.2, 101.9, 93.9, 80.2, 57.8, 40.9; MS (ES+) m/z 462.1 (M + 1). Example 4.83 6-Fluoro-5-methoxy-1·-{[5-(trifluoromethyl)pyran-2-yl]methyl}spiro[1-benzofuran-3,3'-oxime哚]-2\1Ή)-the synthesis of ketone

F Hurricane 'cf3 Following the procedure as described in Example 4, and carrying out irrelevant changes, replacing 2-(bromomethyl) four with 5-bromodecyl-2-(trifluoromethyl)pyrene Hydrogen-2H-pyranose' and replacement of 5,6-dihydrogen with 6-fluoro-5-nonyloxyspiro[1-benzofuran-3,3'-吲哚]-2·(1Ή)-one Snail [benzo[!,2-b : 5,4-b,]difuran-3,3Wh]-2"(1Ή)-ketone' gives 6-fluoro-5-methoxy-oxime-{ [5-(Trifluoromethyl)pyran-2-yl]methyl}spiro[1-benzofuran-3,3'-indole]-2·(1Ή)-one (43%), colorless Solid: melting point 132-134 〇C; 1H NMR (300 MHz, CDC13) δ 7.58 (d, J = 9.4 Hz, 1H), 7.27 143924-sp-20091127-3 -497- 201020257 (dd, J = 7.7, 7.7 Hz, 1H), 7.06-7.01 (m, 2H), 6.84 (d, J = 7.9 Hz, 1H), 6.71-6.67 (m, 2H), 6.62 (d, J = 12.1 Hz, 1H), 6.34 (d , J = 3.4 Hz, 1H), 6.10 (d, J = 3.4 Hz, 1H)' 4.90 (d, J = 16.3 Hz, 1H), 4.57 (d, J = 12.8 Hz, 1H), 4.45 (d, J = 12.7 Hz, 1H), 4.41 (d, J = 16.2 Hz, 1H), 3.91 (s, 3H) ; MS (ES+) m/z 433.9 (M + 1). Example 4.84 Heart-Based-2'-Oxytropia Bufu m-and-phantom] benzodioxolone _7,3W丨Synthesis of ~1'(2Ή)-yl)acetonitrile

Following the procedure as described in Example 4, and carrying out irrelevant changes, the replacement of 2-(bromo-mercapto)tetrahydro-2Η-«-scarnation with gas acetonitrile, and the use of 4,-gas-based snails [2,3-section,3]benzodioxolene-7,3,-ρ?|哚]-2,(1Ή)-ketone replacement 5,6-dihydrospiro[benzo[l,2 -b : 5,4-b']difuran-3,3,-啕哚]-2"(1Ή)-one, obtaining 4,-yl-2-oxo[furo[2,3-f ][l,3] stupid and dioxynene-7,3,-&lt;哚]-Γ(2Ή)-yl)acetonitrile (94%) as a colorless solid: m.p. NMR❹ (300 MHz, DMSO-d6) &lt;5 7.41 (dd, J = 8.0, 8.0 Hz, 1H), 7.27 (d, J = 7.9 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.62 (s, 1H), 6.29 (s, 1H), 5.90 (d, J = 1.9 Hz, 2H), 4.95 (ABq, 2H), 4.79 (ABq, 2H) ; 13 C NMR (75 MHz, DMSO-d6 ) δ 176.4, 156.7, 149.2, 143.0, 141.9, 131.1, 130.4, 128.4, 124.6, 116.8, 115.8, 108.8, 103.3, 101.9, 93.4, 77.6, 58.3, 29.2 ; MS (ES+) m/z 355.2 (M + 1 Example 4.85 Γ-[(2-Amino-1,3-pyrazol-4-yl)indolyl]spiro[furo[2,3-f][U]benzodioxan 143924-sp- 20091127-3 - 498- (8) 201020257 圜-7,3'- indol] -2, (1Ή) - Synthesis of Gang

Following the procedure as described in Example 4, and carrying out an insignificant change, 2-amino-(5-methylmethyl) was used, and 2-(bromoindenyl)tetrahydro-2-indole- Using snails and singularity, phantoms, benzodioxene, oxime, sputum, sputum, ketone, ketone, ketone, ketone, ketone, ketone, ketone, ketone, ketone, ketone ;']二ρ夫喃-3,3'-θ卜朵]_ ® 2&quot;(1Ή)-ketone' obtained Γ-[(2-amino-1,3-, pyrazol-4-yl)曱Snail][2,3-f] [1,3]benzodioxanthene _7,3'- lingual]-2'(1Ή)-嗣(73%), yellow Solid: melting point 230-235 C,1H NMR (300 MHz, DMSO-d6) (5 7.24 (dd,J = 7.7, 7.7

Hz, 1H), 7.12 (d, J = 7.2 Hz, 1H), 7.04-6.96 (m, 2H), 6.93 (s, 2H), 6.65 (s, 1H), 6.37 (s, 1H), 6.22 (s , 1H), 5.89 (s, 2H), 4.76 (d, J = 9.3 Hz, 1H), 4.67-4.59 (m, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.6, 166.8, 155.9, 148.9 , 146.8, 143.9, 142.3, 131.8, 129.6, 129.6, 124.3, 120.3, 109.9, 109.8, (10).1,101.9, 93·9, 80.4, 57.8, 14.8 ; MS (ES+) m/z 394.3 (M + 1) .实例 Example 4.86 4|-Moji-14 (5-carbyl-2-viodinyl)methyl] snail [吱 chew and [23_£][1,3] benzodioxolan-7,3 ,-吲哚]-2,(1,11)-ketone synthesis

Displacement of 2-(bromoindenyl)tetrahydro-211_piper 143924-sp with 2-chloro-5-(chloromethyl)ophenanthrene according to the procedure as described in Example 4 and subject to insignificant changes -20091127-3 -499- 201020257 喃, and use 4'-bromo snail [bito-and [2,3-f][l,3] benzodioxol-7,3'-峋哚] -2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran-3,3'-嘀哚]-2"(1Ή)- Ketone, obtaining Abromo-indenyl-[(5-chloro-2-pyrimenyl)methyl]spiro[吱,[2,3-f][l,3]benzodioxolanesene- 7,3'-Chao 哚]-2'(1Ή)-one (95%) as colorless solid: mp. 85-87 ° C; 4 NMR (300 MHz, DMSO-d6) 57.19-7.11 (m, 2H) , 6.88-6.85 (m, 2H), 6.76 (d, J = 3.8 Hz, 1H), 6.47 (s, 1H), 6.06 (s, 1H), 5.87 (d, J = 5.8 Hz, 2H), 4.97 ( ABq, 2H), 4.91 (d, J = 9.2 Hz, 2H); 13 C NMR (75 MHz, DMSO-dg) δ 176.9, 157.2, 156.9, 149.3, 143.3, 142.1, 136.3, 130.3, 129.8, 127.7, 126.3 , 126.0, 120.2, 116.1, 107.9, 102.6, 101.6, 93.3, 77.2, 59, 5, 39.4; MS (ES+) m/z 490.3 (M + 1), 488.2 (M + 1). Example 4.87 Γ-[( 5-methyl-2-independent thiol] J-keto-l,,2,-dihydrospiro [bito-and-[2,3-f][l,3]benzodioxolene-7,3,_吲哚]_7,_曱Nitrile synthesis

Following the procedure as described in Example 4, and performing an insignificant change, 2-(2-methyl(5-(bromomethyl))tetrahydro-2H piperazine was replaced with 2-methyl-5-(methyl-methyl-cephene) and 2 '-Mercapto-l',2,-dihydrospiro[N,34(^3]benzodioxol-7,3Wbdu]-7'-carbonitrile replacement 5,6 _ Dihydrospiro [benzo[12-7:5 4_b,]difuran-3'3'-W, come to -2&quot;(1'H)-ketone' to obtain 14 (5-carboyl-2-pyrrole) Methyl]_2,__yl-1,2-dihydrospiro[吱,[2,3_f][i,3]benzodioxolene_7 3,_吲哚]_7,_ The carbonitrile (78%) was a colorless solid: m.p. </RTI> </RTI> </RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; = 7.4, 1.1 Hz, 1H), 143924-sp-20091127-3 201020257 7.21 (dd, J = 7.7, 7.7 Hz, 1H), 7.03 (s, 2H), 6.73 (s, 1H), 6.35 (s, 1H ), 5.95 (dd, J = 4.0, 0.7 Hz, 2H), 5.29 (d, J = 1.5 Hz, 2H), 4.78 (dd, J = 20.4, 9.6 Hz, 2H) ; 13C NMR (75 MHz, DMSO- D6) δ 177.0, 155.5, 148.7, 143.2, 141.8, 137.6, 133.6, 133.2, 128.8, 127.9, 126.6, 126.5, 123.7, 118.5, 116.9, 103.0, 101.5, 93.4, 92. 6,79.5, 56.4,40.0 ; MS (ES+) m/z 437.3 (M + 1), 439.3 (M + 1). Example 4.88

Γ-[(2-isopropyl-1,3-pyrazol-4-yl)indolyl]_2,-keto-1,2,-dihydrospiro[吱,[2,3-f] Synthesis of [l,3]benzodioxanthene-7,31_吲哚]·7,_carbonitrile

Follow the procedure as described in Example 4, and perform irrelevant changes

Replacement of 2-(bromomethyl)tetrahydro-2H meridin with 4-(carbomethyl)-2-isopropyl p-serazole and use of 2,-keto-l',2'-dihydrospiro [Bite and [2,34^3] benzodioxanthene -7'34嗓]-7'-phthalonitrile replace 5,6·dihydrospiro[benzo[12:5,4 b, Difuran-3,3W丨哚]-2"(1Ή)-one, obtaining a broad-order isopropyl _u_p- oxazolidine)methyl]_2,·keto-anthracene, 2'-dihydrospiro[ Benzene benzodioxanthene-into 3,啕哚]-7,-carbonitrile (74%) as a colorless solid: m.p. = 162. DMS0-d6) δ 7.66 (dd, J = 8.0, 1.2 Hz, 1H), 7.52 (dd, J = 7.4, 1.2 Hz, 1H), 7.39 (s, 1H), 7.19 (dd, J = 7.7, 7.7 Hz , 1H), 6.72 (s, 1H), 6.42 (s, 1H), 5.94 (s, 2H), 5.25 (ABq, 2H), 4.80 (ABq, 2H), 3.28-3.15 (m, 1H), 1.26 ( d, J = 6.9 Hz, 6H) ; Nmr (75 MHZj DMSO-dg) δ 177.5, 143924-sp-20091127-3 -501 201020257 176.9, 155.4, 149.7, 148.6, 144.0, 141.8, 133.8, 133.1, 128.4, 123.4 , 119.0, 116.5, 114.3, 103.1, 101.5, 93.3, 93.1, 79.4, 56.5, 40.9, 32.4, 22.7 ; MS (ES+) m/z 446.2 (M + 1) 〇 Example 4.89 f Chlorine -Γ-[(5-Gas-2-pyrimenyl)indolyl] snail [吱,[2,3-f][l,3]benzodioxene-7J- 哚]- Ζ(1Ή)-network synthesis

Following the procedure as described in Example 4, and carrying out an insignificant change, 2-(bromomethyl)tetrahydro-2-indole-peryl is replaced with 2-methyl-5-(chloromethyl)-propan. And using 4'-gas-based spiro[吱,[2,3-f][l,3]benzodioxolene-7,3'-吲哚]-2'(1Ή)-嗣5 ,6-dihydrospiro[benzo[1,2-b : 5,4-b1]difuran-3,3'-&lt; 哚]-2"(1Ή)-one, obtaining 4: gas-based -[(5-yl-2-pyrimenyl)methyl] snail [bito-and-[2,3-f][l,3]benzodioxol-7,3,5丨哚] -2·(1Ή)-one (67%) as colorless solid: mp 167-168°C (diethyl ether/hexane); 1H NMR (300 MHz, DMSO-d6) δ 7.36 (dd, J = 8.0, 8.0 Hz, 1H), 7.20-7.18 (m, 2H), 7.08 (dd, J = 8.0, 0.7 Hz, 1H), 6.77 (d, J = 3.4 Hz, 1H), 6.66 (s, 1H), 6.12 (s , 1H), 5.94 (s, 2H), 5.09 (ABq, 2H), 4.92 (d, J = 9.8 Hz, 1H), 4.75 (d, J = 9.8 Hz, 1H) ; 13 C NMR (75 MHz, DMSO -d6) δ 176.1, 156.2, 148.5, 143.3, 141.5, 137.5, 130.5, 129.8, 127.8, 127.7, 127.3, 126.5, 123.6, 116.5, 108.3, 102.4, 101.4, 92.9, 77.0, 57.8, 38.7; MS (ES+) m/z 446.2 (M + 1), 448.2 (M + 1) ° Example 4.90 Gas-l--{[5-(Trifluoromethyl)-2-indolyl]methyl} snail [吱,[2,3-f][l,3] 143924-SP-20091127 -3 • 502- 201020257 Synthesis of benzodioxanthene-7,3,-吲哚]-2,(1,H)-one

啕哚]-2'(1Ή)-_substitution of 5,6-dihydrospiro[benzo[Ub:5,4-7,]difuran_3 3U5丨 using 2-bromomethyl_5_(trifluoromethyl) Substituting 2 (bromomethyl)tetrahydro-2η·pyran, and using 41-gasyl snail [biting benzodioxyl _7,3,_ 哚 哚]-2 (1Ή)-ketone, obtaining 4,_qi-indole-{[5-(trifluoromethyl)-2-furanyl]methyl} snail [biting and sing [2,3&lt;1[1,3] Benzodioxynene _7,34哚]_2. (1, ketone (43%) 'as a colorless solid: iHNMRGOOMHz 'DMSO-de) &lt;5 7.36 (dd, J = 8.0, 8.0 Hz, 1H), 7.20-7.18 (m, 2H), 7.08 (dd, J = 0.7 Hz, 8.0 Hz, 1H), 6.77 (d, J = 3.4 Hz, 1H), 6.66 (s, 1H), 6.12 (s, 1H), 5.94 (s, 2H), 5.09 (ABq, 2H), 4.92 (d, J = 9.8 Hz, 1H), 4.75 (d, J = 9.8 Hz, 1H) ; 13C NMR (75 MHz, DMSO-d6 ) δ 176.1, 156.1, 152.7, 148.6, 143.4, 141.5, 139.5 (q, 2JCF= 42 Hz), 130.5, 129.7, 127.9, 123.6, 118.8 (q, 1 JCF= 267 Hz), 116.6, 114.0 (d, 3 JCF = 3 Hz), ® 109.9, 108.2, 102.2, 101.4, 92.9, 76.9, 57.9, 36.7; MS (ES+) m/z 464.3 (M + 1), 466.3 (M + 1). Example 4.91 4,-gas Base-Γ-[(2-isopropyl-1,3-side) 4-yl)methyl]spiro[吱,[2,3-f][l,3]benzodioxol-7,3'-啕哚]-2'(1Ή)-one synthesis

143924-sp-20091127-3 -503- 201020257 Following the procedure as described in Example 4, and carrying out an insignificant change, replacing 4-(bromomethyl) with 4-(methylmethyl)_2-isopropylthiazole ) tetrahydro-2H_ shouting 'and using 41-chlorospiro[吱,[2,3-f][i,3]benzodioxolene-7,3,_W哚]-2 '(1Ή)-ketone replaces 5,6-dihydrospiro[benzo[l,2-b:5,47']difuran_3,3W丨嗓]-2"(1Ή)-one, which gives 4 ,-Gasyl-1·-[(2-isopropyl_1,3_thorozyl-4-yl)methyl] snail [吱0^ and [2,3-f][l,3]benzo Dioxin _7,3'-'^丨嗓]-2'(1Ή)-one (62%) ' is a colorless solid: mp 147-148 ° C (diethyl ether / hexane); iHNMR (300MHz, DMSO-d6) δ 7.47 (s, 1H), 7.31 (dd, J = 8.0, 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 2H), 6.65 (s, 1H), 6.33 (s, 1H) ), 5.94 (s, 2H), 5.09 (d, J = 16 Hz, 1H), 4.93 (d, J = 9.7 Hz, 1H), 4.91 (d, J = 16 Hz, 1H), 4.76 (d, J = 9.7 Hz, 1H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.5, 176.1, 156.1, 149.5, 148.5, 144.1, 141.4, 130.3, 129.6, 128.1, 123.2, 116.9, 115.2, 108.5, 102.7, 101.4 , 92.8, 76.9, 57.9, 40.2, 32.4, 22.7, 22.6 ; MS (ES+) m/z 455.3 (M + 1), 457.3 (M + 1). Example 4.92 4'-[6-(didecylamino)pyridin-3-yl H,-{[2-( L-methylethyl)_i,3-P-conazole-4-yl]indenyl}spiro[吱,[2,3-f][l,3]benzodioxene-7,3 ,-4哚]-2,(1Ή)-ketone

Follow the procedure as described in Example 4, and carry out irrelevant changes, using 4-(methylmethyl)-2-isopropylcarbazole to replace 2·(bromomethyl)tetrahydro-hydrocarbyl] 143924 -SP-20091127-3 -504- 201020257 喃' and use 4'-[6-(dimethylaminoacridin-3-yl)spiro[吱,[2,3-fl[l,3]benzo Dioxolene-7,3'-啕哚]-2Χ1Ή)-one replaces 5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran_3,3 '4丨哚]-2"(ΓΗ)-ketone, which gives 4'-[6-(diamidoamino)pyridin-3-ylindole'-{[2-(1-methylethyl)-1, 3-oxazol-4-yl]fluorenyl} sulphate[2,3-f][l,3] benzodioxolane _7,3'_呻哚]-2' (1Ή )-ketone (73%) as a colorless solid: m.p. 164-165°C (diethyl ether); 1H NMR (300 MHz, DMSO-d6) 5 7.58 (d, J = 2.3 Hz, 1H), 7.49 (s, 1H ), 7.32 (dd, J = 7.8, 7.8 Hz, 1H), 7.06 (d, J = 7.9 Hz, 1H), 6.82-6.76 (m, 2H), 6.42-6.37 (m, 3H), 5.96 (d, J = 19.0 Hz, 2H), 5.11 (d, J = ® 16.0 Hz, 1H), 4.89 (d, J = 16.0 Hz, 1H), 4.57 (d, J = 9.4 Hz, 1H), 4.42 (d, J = 9.4 Hz, 1H), 3.29-3.20 (m, 1H), 2.99 (s, 6H), 1.31 (d, J = 6.9 Hz, 6H) ; 13C N MR (75 MHz, DMSO-d6) 5 177.5, 176.9, 157.9, 155.4, 149.9, 148.3, 146.6, 142.6, 141.5, 136.8 (2C), 129.2, 128.8, 125.2, 121.7, 121.1, 115.3, 108.6, 104.3, 102.6 , 101.3, 93.2, 77.2, 57.8, 37.6, 32.4, 22.8, 22.7; MS (ES+) m/z 541.3 (M + 1). Example 4.93 Win 3'-[2-(Fluoromethyl)benzyl]- Synthesis of 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,Γ-茚]-2·(3Ή)-one

According to the procedure as described in Example 4, and with irrelevant changes, 1-(indiyl)-2-(ylmethyl)benzene (Kirrnse, W. et al. Org. C/iem. 1994), 59(14): 3821-3829) Displacement of 2-(bromomethyl)tetrahydro-2H-, and use 143924-SP-2009U27-3 -505 - 201020257 with 2,3-dihydrospiro [furo[2,3-g][l,4]benzodioxanthene-8,3^丨哚丨哚]-2'(1Ή)-one substituted 5,6-dihydrospiro[benzo [l,2-b: 5,4-7]difuran-3,3.丨哚]]-2"(1Ή)-ketone, which gives 3'-[2-(fluoromethyl)-yl]-2,3-dihydrospiro[吱,[2,3-§][1 , 4] benzodioxanthene-8,1'-茚]-2'(3'11)-one (53%), as a colorless solid: mp 188-190 ° C; iHNMR (300 MHz, DMSO -d6 )5 7.50 (d, J = 6.6 Hz, 1H), 7.39-7.35 (m, 2H), 7.27-7.15 (m, 3H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.87 ( d, J = 7.8 Hz, 1H), 6.54 (s, 1H), 6.23 (s, 1H), 5.69-5.60 (m, 2H), 5.10-4.98 (m, 2H), 4.76 (ABq, 2H), 4.20 -4.11 (m, 4H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.3, 155.3, 144.7, 142.8, 138.3, 135.3 (d, JC.F = 2.8 Hz), 134.2 (d, JC.F= 15.5 Hz), 132.1, 130.4 (d, JC.F = 7.1 Hz), 130.0 (d, JC.F = 3.3 Hz), 129.3, 128.1, 126.9 (d, JC.F = 1.8 Hz), 124.2, 123.6, 121.5, 111.7, 109.9, 99.3, 82.9 (d, JC.F = 160.6 Hz), 80.1, 64.7, 64.1, 57.8, 55.4; MS (ES+) m/z 439.9 (M +23). Example 4.94 3-[( 2'-keto-2,3-dihydrospiro[吱,[2,3$][1,4]benzodioxanthene-8,3,-吲哚]-1'(2Ή) -Based on the synthesis of benzonitrile

Following the procedure as described in Example 4, and carrying out irrelevant changes, the replacement of 2-(bromomethyl)tetrahydro-2-indole-pyran with α-mo-m-phenylphthalonitrile, and the use of 2,3 -Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3,-蜊哚]-2'(1Ή)-one replaces 5,6-dihydrogen Snail [benzo[1,2-b : 5,4-b,]difuran-3,3,-啕143924-sp-20091127-3 •506- 201020257 哚]-2"(1Ή)-ketone, obtained 3-[(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-吲哚]- Γ(2Ή)-yl)methyl]benzonitrile (66%) as colorless solid: mp 173-178 ° C (ethyl acetate / ethyl ether); 4 NMR (300 ΜΗζ, CDC13) δ 7.60-7.63 (m , 3H), 7.44-7.47 (m, 1H), 7.21-7.24 (m, 2H), 7.05 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 7.5 Hz, 1H), 6.50 (s, 1H), 6.18 (s, 1H), 4.93-4.97 (m, 3H), 4.66-4.69 (m, 1H), 4.13-4.17 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.7, 155.3, 144.8, 141.5, 138.4, 137.4, 132.1, 131.8, 131.7, 130.9, 129.9, 129.0, 124.3, 123.9, 120.7, 118.4, 113.1, 111.4, 108.8, 99.5, ® 80.1, 64.5, 63.9, 58.0, 43.4 ; MS (ES+ ) m/ z 410.8 (M + 1). Example 4.95 Γ-(4-Fluoro-3-methoxybenzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4] Synthesis of benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one

Displacement of 2-(bromomethyl)tetrahydro-2-indole-L'an with 4-(chloromethyl)-1-denyl-2-methoxybenzene and the use of 2,3-dihydrospiro [2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one substituted 5,6-dihydrospiro[benzo[l, 2-b : 5,4-b,]difuran-3,3'-oxime]-2&quot;(1Ή)-ketone' obtains ι'_(4-fluoroyloxyoxybenzyl)-2, 3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3,_吲哚]_2,(1Ή)^ (82%), colorless Solid: melting point 161-163 ° C (hexane); iHNMR pOOMHACDCs) δ 7.23-7.15 (m, 2H), 7.05-7.00 (m, 2H), 6.94-6.77 (m, 3H), 6.49 (s, 1H), 143924-sp-20091127-3 -507- 201020257 6.18 (s, 1H), 5.09-5.04 (m, 1H), 4.97-4.91 (m, 1H), 4.71-4.61 (m, 2H), 4.19-4.08 (m , 4H), 3.83 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 111.6, 155.2, 153.6, 150.4, 148.1, 144.7, 141.9, 138.3, 132.2, 128.8, 124.0, 123.6, 121.0, 119.8, 116.1, 112.4, 111.3, 109.2, 99.5, 79.9, 64.5, 63.9, 58.0, 56.2, 43.8; MS (ES+) m/z 433.8 (M + 1). Example 4.96 4-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-啕哚) ]-Γ(2Ή)-yl) sulfhydryl]

Displacement of 2-(bromomethyl)tetrahydro-2-indole with 4-(,; odorylmethyl)benzonitrile according to the procedure as described in Example 4, and with irrelevant changes, and using 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-啕哚]-(1Ή)-one substitution 5,6 -Dihydrospiro[benzo[l,2-b:5,4-7,]difuran-3,3'-啕哚]-2··(1Ή)-one, 4-[(2'-ketone) Base-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-called 哚]-Γ(2Ή)-yl) Benzoonitrile (85%) as a colorless solid: melting point 69-72 ° C (ethyl acetate / hexane); 4 NMR (300 MHz, CDC13) δ 7.67-7.58 (m, 2H), 7.49- 7.39 (m, 2H), 7.23-7.15 (m, 2H), 7.07-7.00 (m, 1H), 6.69 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.18 (s, 1H) , 5.10 (d, J = 16.1 Hz, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.85 (d, J = 16.1 Hz, 1H), 4.65 (d, J = 9.0 Hz, 1H), 4.22 -4.08 (m, 4H); MS (ES+) m/z 410.9 (M + 1) ° Example 4.97 Γ-(4-isoxazol-5-ylbenzyl)-2,3-dihydrospiro [cough And [2,3-g][l,4]benzodioxane 143924-sp-20091127-3 - 508 - 201020257 urethane-8,3·-吲哚Synthesis of -2, (1Ή)-_

Displacement of 2-(4-(exylmethyl)phenyl)isoxazole (〇2〇g, 〇84 mmol) according to the procedure as described in Example 4, and with irrelevant changes (Misinyl) tetrahydro-2-indole-pyran, and the use of 2,3-dihydrospiro[吱,[2,3-g] φ [1,4]benzodioxanthene-8, 3,-吲哚]-2, (1)-ketone replacement 5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3,-沔丨哚]-2&quot;(1Ή)-ketone, obtaining 1·-(4-isoxazol-5-ylindenyl)-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene-8,3,-啕哚]-2'(1Ή)-one (70%) as a colorless solid: m.p. (: (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) 6 8.28-8.25 (m, 1 Η), 7.77 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.23-7.13 (m, 2H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 6.75 (d, J = 7.8 Hz, 1H), 6.52-6.47 (m, 2H), 6.22 (s , 1H), 5.11 (d, J = 15.8 Hz, 1H), 4.94 (d, J = 8.9 Hz, 1H), 4.84 (d, J = 15.8 Hz, 1H), 4.66 (d, J = _ 8.9 Hz, 1H), 4.22-4.08 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.6, 168.8, 155.3, 150.9, 144.7, 141.9, 138.4, 138.0, 132.2, 128.9, 128.0, 126.9, 126.5, 126.2, 124.1 , 123.6, 120.9, 111.5, 109.2, 99.5, 98.9, 80.2, 64.5, 64.0, 58.1, 43.9, 29.7; MS (ES+) m/z 453.0 (M + 1) 〇 Example 4.98 1·-{[6-(three Fluorodecyl)acridin-3-yl]fluorenyl}-2,3-dihydrospiro [bito-and-[2,3-g][l,4] benzodioxanthene-8,3' -吲哚]-2'(1Ή)-ketone synthesis 143924-sp-20091127-3 •509- 201020257

CF

Following the procedure as described in Example 4, and carrying out an insignificant change, replacing 2-(bromomethyl)tetrahydro-2H_-methane with 5-oxomethyl-2-(trifluoromethyl)pyridine and Use 2,3-one snail [ρ失η南和[2,3_g][i,4]benzodioxanthene -8,3'-啕哚]-2'(1Ή)-one substitution 5 ,6-dihydrospiro[benzo-like seven·5,4-b,]difuran-3,3'-吲哚]-2''(1Ή)-one, obtained ι,_{[6-( Trifluoromethyl racenes_3_yl]decyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3, -吲哚]-2·(1Ή)-ketone (90%) as a colorless solid: m.p. 2〇 4- 207 ° C (di- methane); 1H NMR (300 MHz, CDC13) ¢5 8.74 (d, J = 1.6 Hz, 1H), 7.82 (dd, J = 8.1, 1.6 Hz, 1H), 7.66 (d, J = 8.1 Hz, 1H), 7.27-7.15 (m, 1H), 7.03-7.05 (m, 1H) , 6.75 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.18 (s, 1H), 5.11 (d, J = 16.0 Hz, 1H), 4.92 (d, J = 16.1 Hz, 1H) , 4.91 (d, J = 9.0 Hz, 1H), 4.64 (d, J = 9.0 Hz, 1H), 4.22-4.07 (m, 1H) ; 13C NMR (75 MHz, CDC13) δ 177.7, 155.3, 149.0, 147.9 (q, J = 139.5 Hz), 144.8, 141.2, 138.4, 136.5, 134.9, 132.1 , 129.1, 124.4, 124.1, 121.4, 120.8 (q, J = 10.8 Hz), 120.5, 111.4, 108.6, 99.6, 80.1, 64.5, 63.9, 58.0, 41.3 ; MS (ES+) m/z 429.9 (M + 1) Example 4.99 l'-(4-Isocarbazol-5-ylindenyl)-3-methylspiro[N-[3,2-f][l,2]benzisoxazole-5,3 '-巧丨哚】-2'(1Ή)-ketone synthesis 143924-SP-20091127-3 -510- 201020257

According to the procedure as described in Example 4, and with irrelevant changes, 5-(4-(decylmethyl)phenyl)isoxazole (〇2〇g, 〇84 mmol) was used to replace 2 G stinky.曱 ))) tetrahydro-2H- shouting and using 3_methyl snail [taste π Nanhe [3 2 rhyme 12] benzoisoxazole-5,3'-吲哚]_2, (l, H )-keto-substituted 5,6-dihydrospiro[benzo[i,2-b: 〇5,4-7']disodium-3,34哚]_2"(1Ή)-one, obtaining 1,-( 4-isoxazol-5-ylbenzyl)-3-methylspiro[吱,[3,2-f][i,2]benzoiso-u, _5,3'_吲嗓]_2 ·(1Ή)-ketone (60%) ' is colorless solid: melting point ^2-194^; 4 NMR (300 MHz, DMSO-d6) δ 8.25 (d, J = 1.8 Hz, 1H), 7.81 (d, J = 8.3 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H), 7.47 (d, J = 8.6 Hz, 1H), 7.27-7.09 (m, 2H), 7.02-6.95 (m, 2H), 6.75 (d, J = 7.8 Hz, 1H), 6.50 (d, J = 1.8 Hz, 1H), 5.32 (d, J = 16.2 Hz, 1H), 5.15 (d, J = 9.1 Hz, 1H), 4.89 (d , J = 9.1 Hz, 1H), 4.83 (d, J = 16.2 Hz, 1H), 2.45 (s, 3H) ; 13 C NMR (75 MHz, DMSO-^) δ 176.3,169.0, 164.0,158.2, ® 155.0 , 150.8, 141.9, 137.4, 130.5, 129.4, 127.8, 126.8, 123.8, 123. 7, 123.1, 118.0, 109.7, 108.9, 108.0, 98.9, 81.4, 56.4, 53.5, 44.1, 9.8; MS (ES+) m/z 449.9 (M + 1). Example 4.100 Γ-[(5-fluoropyridine) -2-yl)methyl]_2,3-dihydrospich and [2,3_g][1,4]benzodioxene-8,3^哚]-2'(1Ή)- Synthesis of ketones 143924-sp-20091127-3 -511- 201020257

2-(Gasylmercapto)-5-fluoropyridine hydrochloride (Cai, z et al. us 2〇〇7/ 0072831) was used according to the procedure described in Example 4, and irrelevant changes were applied. Displacement of 2-(bromomethyl)tetrahydro-2H-«, and the use of 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene _8,3,_吲哚]_2,(ΓΗ)-ketone replaces 5,6-dihydrospiro[benzo[l,2-b:5,47']difuran-3,3,-啕哚]-2&quot;(1Ή)-ketone, which gives Γ-[(5-fluoropyridin-2-yl)methyl]-2,3-dihydrospiro [bito-[2,34][1,4] Benzodioxanthene-8,3'-throindolin-2'(1Ή)-one (99%) is a colorless solid: mp 174-176. (:; 1H NMR (300 MHz, CDC13) δ 8.40 (d, J = 2.7 Hz, 1H), 7.41-7.11 (m, 4H), 7.01 (t, J = 7.4 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.48 (s, 1H), 6.25 (s, 1H), 5.16 (d, J = 15.7 Hz, 1H), 4.98-4.88 (m, 2H), 4.65 (d, J = 8.9 Hz , 1H), 4.20-4.07 (m, 4H); 13C NMR (75 MHz, CDC13) 6 177.5, 160.2, 157.2, 155.3, 151.5, 151.5, 144.7, 142.0, 138.3, 137.8, 137.5, 132.2, 128.8, 124.1, 123.9, 123.8, 123.6, 122.9, 122.8, 121.0, 111.6, 109.4, 99.4, 80.1, 64.5, 63.9, 58.1, 45.4; MS (ES+) m/z 404.9 (M + 1). Example 4.101 Γ-[(3- Fluoropyridin-2-yl)indolyl]-2,3-dihydrospiro[pf-rano[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-ketone synthesis

143924-sp-20091127-3 -512- 201020257 According to the procedure as described in Example 4, and with irrelevant changes, 2-(methylmethyl)-3-pyridylpyridine hydrochloride (Weidmann, κ) was used. Et al., J. Med. (1992), (35): 438) Displacement of 2-(bromomethyl)tetrahydro-2H-'-, and use of 2,3-dihydrospiro[吱? 2,3-g][l,4]benzodioxanthene_8,3,_啕哚]_2,(1'H)-_ replaces 5,6-a wind snail [benzo[l, 2-b : 5,4-b']dipyran-3,3'-p?丨嗓]-2,'(1Ή)_ketone' obtains 1'-[(3-fluoropyridine-2-yl) )methyl]-2,3-dihydrospiro[sn-[2,3-g][l,4]benzodioxanthene_8,3'_吲哚]·2,(1Ή) , (25%), as colorless solid: mp 247-249 ° C (dioxane / ether); 1 η NMR (300 MHz, CDC13) β δ 8.35 (td, J = 4.6, 1.34 Hz, 1H), 7.43-7.33 (m, 1H), 7.27-7.11 (m, 3H), 7.02-6.95 (m, 1H), 6.80-6.75 (m, 1H), 6.47 (s, 1H), 6.44 (s, 1H), 5.31 (dd, J = 16.2, 1.5 Hz, 1H), 5.04 (dd, J = 16.2, 1.4 Hz, 1H), 4.95 (d, J = 8.9 Hz, 1H), 4.67 (d, J = 8.9 Hz, 1H ), 4.20-4.07 (m, 4H); 13 c NMR (75 MHz, CDCl3) &lt;5 177.5' 159.6, 156.2, 155.2, 145.4, 145.3, 144.5, 142.9, 142.8, 142.2, 138.3, 132.6' 128.6, 124.3, 123.8, 123.3, 123.1, 121.3, 112.2, 109.0, 99.2, 80.2, 64.5, 63.9, 58.1, 40.7; MS (ES+) m/z 404.7 (M + 1). _ example 4.102

R-(Acridine-2-ylindenyl H,-4oxalin-3-yl-2,3-dihydrospiro[味D南和[2,3-g][1,4]benzodioxan The synthesis of terpene-8,3,-啕哚]-2,(1Ή)-one was carried out according to the procedure as described in Example 4, and the insignificant change was performed 143924-sp-20091127-3 -513- 201020257 using 2 -(明基曱基) Acridine hydrobromide replaces 2-(bromomethyl)tetrahydro-2H-pyranose and uses 4'-quinolin-3-yl-2,3-dihydrospiro Fusino[2,3-g][l,4]benzodioxanthene-8,3^5丨哚]-2'(1Ή)-one substituted 5,6-dihydrospiro[benzo [i,2-b : 5,4-b']difuran-3,3'-throindole]-2"(1Ή)-one, Γ-〇pyridin-2-ylmethyl)-4' -p quinolin-3-yl-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene_8,3i-啕哚]_ 2'( 1Ή)-ketone (73%) as a colorless solid: 228-230 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 10.70 (s, 1 Η), 7.42-7.32 (m , 2H), 7.26 (t, J = 7.8 Hz, 1H), 7.13-7.05 (m, 1H), 6.96-6.90 (m, 3H), 6.79-6.70 (m, 5H), 6.23 (s, 1H), 6.12 (s, 1H), 4.47 (d, J = 9.3 Hz, 1H), 4.32 (d, J = 9.3 Hz, 1H), 4.15-4.01 (m, 4H) ; 13C NMR (75 MHz, CDC13) &lt;5 177.8, 155.4, 150.3, 149.6, 147.2, 144.8, 142.7, 138.2, 137.2, 136.4, 135.7, 131.2, 130.4, 129.2, 128.0, 126.9, 125.9, 122.9, 122.7, 121.8, 111.3, 109.5, 99.6 , 64.6, 64.1, 46.3; MS (ES+) m/z 513.9 (M + 1) 〇 Example 4.103 4H4-Phenoxyphenyl)-i'_(pyridine-2-ylmethyl)_2,3_dihydrogen Snail [biting and [2,3-g][l,4] benzodioxanthene _8,3LlI?| ρ stay]_2, (ΓΗ) network synthesis

Following the procedure as described in Example 4, and carrying out an insignificant change, 2-(bromo-mercapto-hydroridinium hydrobromide was substituted for 2_(bromomethyl)tetrahydro-2 Η 143924-SP-20091127- 3 •514· 201020257 ,, and using 4'-(4-phenoxyphenyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Terpene-8,3W丨哚]-2'(1Ή)-one substituted 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran_3,3,5丨哚]-2"(1Ή)-ketone, which gives 4'-(4-phenoxyphenyl)-indole-(acridin-2-ylmethyl)-2,3-dihydrospiro[吱[2,3-g][l,4]benzodioxanthene-8,3|-啕哚]-(1 condition)-ketone (90%), colorless solid: melting point 196-199 °(:(dichloromethane/ether); 4 NMR (300 MHz, CDC13) 5 8.61-8.57 (m,1H), 7.69-7.65 (m, 1H), 7.40-7.18 (m, 5H), 7.12-7.05 (m, 1H), 7.02-6.97 (m, 2H), 6.93-6.86 (m, 2H), 6.84-6.71 (m, 4H), 6.39 (s, 1H), 6.21 (s, 1H), 5.26 (d , J = 15.8 Hz, ® 1H), 4.95 (d, J = 15.8 Hz, 1H), 4.73 (d, J = 9.0 Hz, 1H), 4.43 (d, J = 9.0 Hz, 1H), 4.20-4.07 ( m, 4H); 13C NMR (75 MHz, CDC13) &lt;5 178.2, 157.4, 156.3, 155.6, 149.6, 144.7 , 142.4, 139.8, 137.9, 137.1, 133.5, 130.4, 130.1, 129.7, 128.7, 125.4, 123.1, 122.8, 122.3, 121.7, 118.6, 118.4, 111.2, 108.7, 99.3, 77.9, 64.5, 64.0, 58.5, 46.2; (ES+) m/z 555.0 (M + 1). Example 4.104 1·-[(3,5-Difluorop-biti-2-yl)methyl]-2,3-dihydrospiro[pfnan Synthesis of [2,3_g][i,4]benzodioxanthene-8,3·-吲哚]-2'(1Ή)-one

The 2-(chloromethyl)-3,5-difluoropyridine hydrochloride was substituted for 2-(bromomethyl)tetrahydro-2-indole according to the procedure as described in Example 4, and the insignificant change was carried out. , exhibition, and the use of 2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxene-8,3'-呻哚]-2·(1Ή)- Ketone replacement of 5,6-dihydrospiro [benzo[[7:5,4-b,]difuran 143924-sp-20091127-3 515- 201020257 -3,3'-沔h]-2" (1Ή )-ketone, obtained Γ-[(3,5-difluorophenanthyl-2-yl)indenyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzene Dioxodecene-8,3'-W哚]-indole (-)-ketone (64%) as colorless solid: m.p. 220-222°C (ethyl acetate/hexane); WNMR (300 MHz , CDC13) δ 8.27 (d, J = 1.7 Hz, 1H), 7.26-7.11 (m, 3H), 7.04-6.96 (m, 1H), 6.77 (d, J = 7.7 Hz, 1H), 6.49-6.46 ( m, 1H), 6.39-6.36 (m, 1H), 5.27 (d, J = 16.1 Hz, 1H), 5.00 (d, J = 16.1 Hz, 1H), 4.95-4.90 (m, 1H), 4.68-4.63 (m, 1H), 4.20-4.06 (m, 4H); 13C NMR (75 MHz, CDC13) δ 177.5, 159.7, 156.2, 155.3, 144.6, 142.0, 139.0, 138.9, 138.3, 133.8, 133.6, 132.5, 123.9, 123.4, 121.2, 112.0, 111.6, 108.9 , s., s., s. Synthesis of 2·-Dihydrospiro[1-benzofuran-3,3·-吲哚]-6-carbonitrile

According to the procedure as described in Example 4, and with irrelevant changes, 2-(bromomethyl)acridine hydrobromide was used to replace 2_(bromomethyl)tetraindole-2H_&lt; 喃' and use 2 '-keto-1,2,-dihydrospiro[1-benzofuran-3,3'-呻哚]-6-carbonitrile displaces 5,6-dihydrospiro[benzo[i,2- b : 5,4-b,]difuran-3,3'-啕哚]-2,, (1Ή)-sun, obtaining 2'-keto-1'-(pyridin-2-ylmethylχτ- Dihydrospiro[1-benzofuran_3,3,-anthracene-6-indolecarbonitrile (89%) as colorless solid: m.p.: 151-153 (c/hexane); 1H NMR (300 MHz, CDC13 ) δ 8.55 (d, J = 3.9 Hz, 1H), 7.66 (t, J = 7.5 Hz, 143924-sp-20091127-3 -516- (8) 201020257 1H), 7.34-6.84 (m, 9H), 5.19 (d , J = 15.8 Hz, 1H), 5.07 (d, J = 9.2 Hz, 1H), 4.97 (d, J = 15.8 Hz, 1H), 4.79 (d, J = 9.2 Hz, 1H) ; 13C NMR (75 MHz , CDC13) δ 176.3, 160.7, 155.1, 149.7, 142.3, 137.1, 134.8, 131.2, 129.5, 125.8, 124.6, 123.8, 122.9, 121.8, 118.5, 113.8, 113.3, 109.9, 80.21, 77.5, 57.9, 46.1; MS ( ES+) m/z 353.9 (M + 1). Example 4.106 Alkene 3-{[(8S)-2·-keto-2,3-dihydrospiro[吱Synthesis of [2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-1·(2Ή)-yl]methyl}benzonitrile

❹ ❹ using 2-(Molylmethyl)benzonitrile to replace 2-(bromomethyl)tetrahydro-2 Η-' smear, according to the procedure described in Example 4, and performing irrelevant changes, and Using (8S)-2,3-dihydrospich-[2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-2·(1Ή) - Ketone replacement of 5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difurone]-2&quot;(ΓΗ)-ketone' to obtain 3-{[(8S)- 2,-keto-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8,3'-"哚"-Γ(2Ή) -yl]methyl}benzonitrile (75%) as a colorless solid: m.p. 94-96 ° C (isopropanol); 4 NMR (300 MHz, CDC13) &lt;5

7.65-7.52 (m, 4H), 7.49-7.42 (m, 2H), 7.23-7.15 (m, 1H), 7.08-7.01 (m, 1H), 6.75-6.70 (m, 1H), 6.49 (s, 1H ), 6.18 (s, 1H), 5.03 (d, J = 15.8 Hz, 1H), 4.95-4.84 (m, 2H), 4.66 (d, J = 9.0 Hz, 1H), 4.20-4.07 (m, 3H) ; 13 C NMR (75 MHz, CDCI3) 5 177.6, 155.3, 144.8, 141.5, 138.4, 137.4, 132.1, 131.8, 130.9, 129.9, 129.0, 124.3, 123.9, 120.7, 118.4, 113.1, 111.4, 108.8, 99.5, 80.1 , 64.5, 63.9, 58.0, 43.4, 29.7; MS (ES+) m/z 411.0 (M + 1) 〇 143924-sp-20091127-3 -517- 201020257 C2 Analysis of 5Hi8N2〇4: c, 73.16; H, 4.42; N, 6.83. Found: C, 72.92; H, 5.05; N, 6.50. Example 4.107 (8S)-l'-[(5-Fluoro-p-But-2-yl)indenyl]-2,3-dihydrospiro[吱嗔,[2,3_g][14]benzodioxine Synthesis of Lu Wei-8,3'-»»5丨朵]-2'(ΓΗ)-ketone

According to the procedure as described in Example 4, and the insignificant change was carried out, the use of 5-(methylmethyl)-2-fluoroylpyridine hydrochloride to displace 2-(bromomethyl)tetrahydro- 2Η-* Trace' and use (8S)-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxene-8,3'-吲哚]-2·(1Ή)-ketone replacement 5,6-dihydrospiro[benzo[i,2-b : 5,4-b']difuran-3,3'-蚓哚]-2" (1Ή )-ketone, (8S)-l'-[(5-fluoropyridin-2-yl)methyl]-2,3-dihydrospiro[,,[2,3-g][l,4 Benzodioxanthene _8,3'-呻哚]-2'(1Ή)-one (68%) as colorless solid: m.p. 210-212°C (isopropanol); 1HNMR (300 MHz , CDC13) δ 8.40 (d, J = 2.6 Hz, 1H), 7.41-7.11 (m, 4H), 7.05-6.97 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.25 (s, 1H), 5.16 (d, J = 15.7 Hz, 1H), ^ 4.99-4.88 (m, 2H), 4.65 (d, J = 8.9 Hz, 1H), 4.20-4.06 (m, 4H) ; 1 3 C NMR (75 MHz, CDCI3) δ 177.5, 160.6, 157.2, 155.3, 151.5, 144.7, 142.0, 138.3, 137.8, 137.5, 132.2, 128.8, 124.1, 123.9, 123.8, 123.6, 122.9, 121.0, 111.6, 109.4, 99.4, 80.1, 54.5, 63.9, 58.1, 45.4 ; M For the analysis of C23H17N204: C, 68.31; H, 4.24; Ν, 6.93. Found: C, 67.81; Η, 4.39; Ν, 6.85. Example 4.108 and Example 4.109 143924-sp-20091127-3 -518- (8) 201020257 (8SH4(3-Fluoropyridine-2-yl)indolyl]_2,3_dihydrospiro[吱,[2,3_g][ 14] benzodioxantemene-8,3'-啕哚]-2, (1Ή)-one and (3) ketobutyl)-3,7-dichloro-2H-spiro [benzofuran [ 5,6_,4]Dioxane decene _8,3,indoline]_2, ketone synthesis

φ In accordance with the procedure as described in Example 4, and insignificantly changing, 2-(methylmethyl)&gt; 3-fluoropyridine hydrochloride was substituted for 2-(bromomethyl)tetrahydro-2H-piperidin And '(8S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2, (1Ή)-ketone replacing 5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-吲哚]-2"(1Ή)-one, Obtained -1,-[(3-decylpyridin-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodiox Lucene-8,3|-吲哚]-2,(1)-鲷(33%)' is a colorless solid: melting point 125-126 ° C (diethyl ether); iHNMRGOOMHz, CDC13) (5 8.38-8.32 ( m, 1H), 7.43-7.34 (m, 1H), 7.28-7.11 (m, 3H), 7.02-〇6.95 (m, 1H), 6.78 (d, J = 7.6 Hz, 1H), 6.48 (s, 1H) ), 6.44 (s, 1H), 5.31 (d, J = 16.2 Hz, 1H), 5.04 (d, J = 16.2 Hz, 1H), 4.95 (d, J = 8.9 Hz, 1H), 4.67 (d, J = 8.9 Hz, 1H), 4.21-4.07 (m, 4H); 13C NMR (75 MHz, CDC13) (5 177.5, 159.6, 156.2, 155.2, 145.4, 144.5, 142.9, 142.8, 142.2, 138.3, 132.6, 128.6, 124.3, 123.8, 123.3, 123.1, 121.3, 112.2, 109.0, 99 .2, 80.2, 64.5, 63.9, 58.1, 40.7; MS (ES+) m/z 404.9 (M + 1). Calculated for C23H17FN204: C, 68.31; Η, 4_24; N, 6.93. Found: C , 67.27; Η, 4.24; N, 6.93. Isolation (3)-Guang (2-ketobutyl)-3,7-dihydro-2 snail [benzofuran [5,6-7] 143924- Sp-20091127-3 -519- 201020257 [1,4]dioxolene-8J-dihydrothroquinone-2'-one (6%), a by-product from this reaction, is a colorless solid: 182-183°C (diethyl ether); NMROOOMHz, CDC13) δ 7.28-7.20 (m, 1H), 7.17 (d, J = 7.2 Hz, 1H), 7.07-7.00 (m, 1H), 6.63 (d, J = 7.8 Hz, 1H), 6.47 (s, 1H), 6.37 (s, 1H), 4.89 (d, J = 9.0 Hz, 1H), 4.68-4.56 (m, 2H), 4.44 (d, J = 17.9 Hz, 1H), 4.20-4.07 (m, 4H), 2.54 (q, J = 7.3 Hz, 2H), 1.11 (t, J = 7.3 Hz, 3H) ; 13 C NMR (75 MHz, CDC13) &lt;5 203.5, 177.6, 155.2, 144.6, 141.9, 138.4, 132.2, 128.8, 124.0, 123.7, 120.9, 111.9, 108.2, 99.3, 80.0, 64.5, 63.9, 58.0, 48.9, 33.2, 7.4; MS (ES+) m/z 366.0 (M + 1). Example 4.10 Γ-[(4-Fluorofluorenyl)-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Synthesis of terpene-8,3'-吲哚]-2·(1Ή)-_

Following the procedure as described in Example 4, and performing an insignificant change, _ 2-(carbomethyl)-4-fluoropyridine hydrochloride was used to replace 2_(bromomethyl)tetrahydro-2Η- And use 2,3-dihydrospiro [biting and [2,3_g off, 4] benzodioxanthene -8,3'-4h]-2'(1Ή)-ketone replacement 5, 6-Dihydrospiro[benzo[i,2_b :5,4-b,]difuran-3'3'-decade]-2&quot;(1Ή)-ketone' obtains ι'|fluoro-based ρ-pyridine 2_yl)methyl]_2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxolene_8,3,_ρ5丨哚]_2, (1Ή ) ketone (54%) ' is a colorless solid: mp 228 </ RTI> </ RTI> </ RTI> (diethyl ether); lH NMR (3 〇〇 MHz, CDCI3) δ 8.52 (dd, J = 8.38, 5.56 Hz, 1H), 7.24-7.14 (m, 2H ), 7.06-6.90 (m, •520- 143924-sp-20091127-3 (S) 201020257 3H), 6.85 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.30 (s, 1H) , 5.15 (d, J = 16.0 Hz, 1H), 5.02-4.91 (m, 2H), 4.67 (d, J = 8.9 Hz, 1H), 4.21-4.07 (m, 4H) ; 13C NMR (75 MHz, CDC13 ) δ 177.6, 171.0, 167.6, 158.9 (2), 155.3, 152.0 (2), 144.7, 141.9, 138.4, 132.2, 128.9, 124.0, 123.7, 120.9, 111.7, 111.0, 110.8, 109.7, 109.5, 109.3, 99.4, 80.1, 64.5, 63.9, 58.1, 45.8, 11.9; MS (ES+) m/z 404.9 (M + 1). Example 4.11 Γ-(2,3-Dihydro-1,4-benzodioxanthene-6-ylmethyl)_2,-ketodihydrospiro[1-benzofuran-3,3·- Synthesis of 嘀哚]-6-carbonitrile

Using 6-(chloromercapto)-2,3-dihydrobenzo[^,4]dioxene terpene (Capilla, A S according to the procedure described in Example 4) and performing irrelevant changes Et al. (2001), 57: 8297) Displacement of 2-(bromomethyl)tetrahydro-2H-piperidin and use of 2'-mercapto-1'-(pyridin-2-ylmethyl) -Γ,2·-Dihydrospiro[1-benzofuran-3,3·-吲嗓]-6-carbonitrile displaces 5,6-dihydrospiro[benzopyrene:5,4-b,] Difuran-3,3,-吲哚]-2"(1Ή)-one, 1'-(2,3-dihydro-1,4-benzodioxanthenemethyl)-2 -keto-anthracene, 2'-dihydrospiro[1-benzofuran_3,3,_4丨哚]_6-carbonitrile, colorless solid · melting point 181-183 ° C (di-methane/diethyl ether) iH NMR (300 MHz, CDC13) δ 7.29-7.16 (m, 1H), 7.15-6.97 (m, 3H), 6.89-6.75 (m, 5H), 5.04 (d, J = 9.2 Hz, 1H), 4.94 (d, J = 15.3 Hz, 1H), 4.80-4.67 (m, 2H), 4.25-4.19 (m, 4H); 13C NMR (75 MHz, CDC13) δ 176.2, 160.8, 143.8, 143.3, 142.2, 143924- Sp-20091127-3 •521 · 201020257 134.7, 131.3, 129.5, 128,5, 125.8, 124.4, 123.8, 123.7, 120.5, 118.5, 117.8, 116.3, 113.8, 113.3, 109.8, 80.2, 64.3 (2 C), 57.8, 43.8. Example 4.12 Γ-[(3-Chloropyridin-2-yl)methyl]-2,3-di argon [唉,[2,3-g][l,4] Synthesis of benzodioxanthene-8,3'-吲嗓]-2'(1Ή)-one

Following the procedure as described in Example 4, and performing an insignificant change, the replacement of 2-(bromodecyl)tetrahydro-2-indole with 3-methyl-2-(ylmethyl)pyridine hydrochloride And, using 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-吲哚]-2'(1Ή)- Purine substitution of 5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,34哚]-2"(1Ή)-ketone' to obtain Γ-[(3- Phenylpyridine-2-yl)indenyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene]-2'(1Ή) -_

(67%) 'Colorless solid: melting point 176-178 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 8.35-8.31 (m, 1H), 7.47 (d, J = 7.6 Hz , 1H), 7.27-7.15 Q (m, 3H), 7.09-7.02 (m, 1H), 6.75 (d, J = 7.8 Hz, 1H), 6.50 (d, J = 1.5 Hz, 1H), 6.23 (d , J = 1.4 Hz, 1H), 5.13 (d, J = 16.8 Hz, 1H), 5.02-4.89 (m, 2H), 4.67 (dd, J = 8.9, 1.3 Hz, 1H), 4.22-4.06 (m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 177.8, 155.4, 150.0, 148.9, 144.8, 141.4, 138.4, 136.9, 132.0, 129.1, 129.8, 124.2, 124.0, 123.0, 120.6, 111.4, 109.1, 99.6, 80.2 , 64.5, 63.9, 58.1, 41.2. Example 4.13 1'-[2-(Trifluoromethyl)methyl]-2,3-dihydrospiro[Octa[2,3-g][l,4]benzodioxol 143924-sp- 20091127-3 -522- (8) 201020257 Gardening ·8,3'·吲哚]-2,(1Ή)-ketone synthesis

Purification of 2 (bromomethyl)tetrahydro-2η_pipeper with 1-(methylmethyl)-2-(trifluoromethyl)benzene according to the procedure described in Example 4 and subject to insignificant changes And, using 2,3-dihydrospiro[N,3_g][14]benzodioxanthene-8,3,-吲哚]-2,(1Ή)-one substitution 5, 6-Dihydrospiro[benzo[127:5 4 b,]difuran-3,3'-吲哚]-2&quot;(1Ή)-ketone' obtained 142_(trifluoromethyl)-yl]_2 3 _ Dihydrospiro[唉,[2,3-g][l,4]benzodioxolene _8,3,_,哚]_2ι(1Ή)-ketone (55%) as a colorless solid : melting point 207-208 ° C (di-methane / diethyl ether); 4 NMR (300 MHz, CDC 13) δ 7.72 (d, J = 7.6 Hz, 1H), 7.51-7.42 (m, 2H), 7.42-7.34 (m , 3H), 7.22-7.12 (m, 1H), 7.07-7.00 (m, 1H), 6.61 (d, J = 7.7 Hz, 1H), 6.52 (s, 1H), 6.31 (s, 1H), 5.26 ( d, J = 17.1 Hz, 1H), 5.07 (d, J = 17.0 Hz, 1H), 4.97 (d, J = 8.9 Hz, 1H), 4.70 (d, J = 8.9 Hz, 1H), 4.24-4.09 ( m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 111.9, 155.4, 144.8, 141.8, 138.4, 133.9, 132.5, 132.1, 129.0, 128.3 (q, J = 30.8 Hz), 127.7, 126.8, 126.4 (q , J = 5.8 Hz), 124.4 (q, J = 273.7 Hz), 124.1, 123.8, 120.8, 111.5, 109.2, 99.5, 80.3, 64.5, 63.9, 58.2, 40.6 ; MS (ES+) m/z 454.1 (M + 1) 0 Example 4.114 (8R -l'-[2-(Trifluoromethyl)-yl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 ,3 W丨哚]-2'(1 Ή)-嗣的合成143924-SP-20091127-3 • 523- 201020257

Following the procedure as described in Example 4, and carrying out irrelevant changes, replacing 2-(bromodecyl)tetrahydro-2H_ brigade with 1-(bromomethyl)-2-(trifluoromethyl)benzene • South, and use (8 feet)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-M丨哚] -2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran

-3,3Ί 嗓]-2"(1Ή)-ketone, obtain (8R)-r-[2-(tri-f-methyl)-yl]-2,3-dihydro-A snail [吱°南和[ 2,3-g][l,4]benzodioxanthene _8,3,-m pudol]-2,(1Ή)-ketone (87%) ' is a colorless solid: melting point 137-138° C (ether); 1H NMR (300 MHz, CDC13) δ 7.72 (d, J = 7.6 Hz, 1H), 7.52-7.33 (m, 2H), 7.22-7.13 (m, 3H), 7.07-7.00 (m, 1H), 6.62 (d, J = 7.8 Hz, 1H), 6.52 (s, 1H), 6.31 (s, 1H), 5.26 (d, J = 17.1 Hz, 1H), 5.08 (d, J = 17.1 Hz, 1H), 4.97 (d, J = 8.9 Hz, 1H), 4.70 (d, J = 8.9 Hz, 1H), 4.23-4.09 (m, 4H) ; 1 3C NMR (75 MHz, CDC13) δ 177.9, 155.4, 144.8, 141.8, 138.4, 133.9, 132.5, 132.1, 129.0, 127.9 (q, 2Jc.f = 30.8 Hz), 127.6, 126.8, 126.4 (q,5 JC-f= 5.8 Hz), 124.4 (q, 1 JC- F = φ 273.8 Hz), 124.1, 123.8, 120.8, 111.6, 109.2, 99.6, 80.3, 64.5, 64.0, 58.2, 40.6 (q, J = 3.4 Hz); MS (ES+) m/z 454.0 (M + 1) Analysis of C2 5 Η! 8 F3 N04: C, 66.22; H, 4.00; N, 3.09. Found: C, 66·16; H, 4.11; N, 3.07. Example 4.115 5'-Methyl -Γ-{[3-(trifluoromethyl) ratio -2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3W丨哚]-2' ( 1Ή)-- Synthesis 143924-sp-20091127-3 • 524· (8) 201020257

The 2-(chloromethyl)-3-(trifluoromethyl)pyridine hydrochloride was used to replace 2-(bromomethyl)tetrahydro- in accordance with the procedure described in Example 4 and the insignificant changes were made. 2H-pyran, and the use of 5,-mercapto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3*-呻哚]-ΑΓΗ)-ketone replacement 5,6-dihydrospiro[benzoxanthene [Hb: 5,4-b·]difuran-3,3·-吲哚]-2&quot;(1Ή&gt; ketone, obtained ( 5,-Methyl-1,-{[3_(trifluoromethyl)acridin-2-yl]indolyl}-2,3-dihydrospiro [bito-and-[2,3-g][l, 4] benzodioxanthene-8,3'-啕哚]-2·(anthracene)-one (62%) as colorless solid: mp 137-139 ° C (diethyl ether); 1H NMR (300 MHz, DMSO -de) (5 8.63 (d, J = 4.6 Ηζ, 1Η), 8.22 (d, J = 7.5 Hz, 1H), 7.57-7.50 (m, 1H), 7.02-6.94 (m, 2H), 6.72 (d , J = 7.9 Hz, 1H), 6.47 (s, 1H), 6.40 (s, 1H), 5.29-5.03 (ABq, 2H), 4.76-4.64 (ABq, 2H), 4.18-4.06 (m, 4H), 2.18 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) &lt;5 177.4, 155.0, 153.0, 152.9, 144.5, 140.9, 138.2, 135.5 (q, 4J = 5.31 Hz), ® 132.5, 132.5, 1293 , 124.5, 124.4 (q,li = 273.6 Hz), 1 23.5 (q, 2J = 32.3 Hz), 123.5, 122.2, 112.3, 109.3, 99.1, 79.7, 64.7, 64.1, 57.8, 42.4 (q, J = 3.1 Hz), 21.0 ; MS (ES+) m/z 469.0 (M + 1) Example 4.16 (8S)-142-(Trifluoromethyl)-yl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Synthesis of terpene-8,3'-吲哚]-2\1Ή)-ketone 143924-sp-20091127-3 525- 201020257

According to the procedure as described in Example 4, and irrelevant changes were made, 2·(trifluoromethyl) desertification benzyl substitution 2_(bromo fluorenyl hydrazine, and (8S)-2 was used. ,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene_8,3,-吲嗓]-2'(1Ή)-one substituted 5,6-di Hydrogen snail [benzo[1,2-7:5,4-7,]difuran-3,3,-p-bend]-2&quot;(1Ή)-ketone' obtained (8S&gt;1,_[2_$fluorine曱 芹 ] ] ] ] ] 咬 咬 咬 咬 咬 2 2 2 2 2 2 2 [2,3-§][1,4] benzodioxanthene _8,3,-嘀哚]_2, (1,11 )-ketone (82%) as colorless solid: mp 137-138 ° C (ethyl ether); 1H NMR (300 MHz, CDC13) 5 7.72 (d, J = 7.7 Hz, 1H), 7.52-7.33 (m, 2H ), 7.22-7.12 (m, 3H), 7.07-7.00 (m, 1H), 6.61 (d, J = 7.7 Hz, 1H), 6.52 (s, 1H), 6.31 (s, 1H), 5.26 (d, J = 17.1 Hz, 1H), 5.07 (d, J = 17.1 Hz, 1H), 4.97 (d, J = 8.9 Hz, 1H), 4.70 (d, J = 8.9 Hz, 1H), 4.23-4.09 (m, 4H) ; 13C NMR (75 MHz, CDC13) 5 177.9, 155.4, 144.8, 141.8, 138.4, 133.9, 132,5, 132.1, 129.0, 127.9 (q, 2JC-F = 30.8 Hz), 127.6, 126.8, 126.4 ( q, 5JC-F= 5.8 Hz), 124.4 (q, 1 JC-F= 273.8 Hz), 124.1, 123.8, φ 120.8, 111.6, 109.2, 99.6, 80.3, 64.5, 64.0, 58.2, 40.6 (q, J = 3.4 Hz) ; MS (ES+)m/z454.0( M+l); calcd for C25H18F3N04: C, 66.22; H, 4.40; N, 3.09. Found: C, 66.06; H, 3.98; N, 3.12 ° Example 4.17 4'-Bromo-indole-( Pyridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][M]benzodioxanthene-8,3,-(f)哚]_2'(1Ή )-嗣的合成-526- 143924-sp-20091127-3 (S) 201020257

❹ Press ..., as described in Example 4, and perform irrelevant changes, using 2 (Guangji-based wind-bite hydroquinone replacement machine-based methyl group), four-gas nucleus and 4-sided group- 2,3-Dihydrospiro[吱,[2,3 g][1,4]benzodioxanthene 8'3 5丨;^ ]-2 (1H)-ketone replacement 5,6_2 Hydrogen snail [benzo[5:4 b,] two bite drink -3,3,-·2,,(1Ή)_嗣, obtain μ-base _lH(tetra)_2-ylmethyl)_2,3_diox[矢南和[2,3-g][l,4]benzodioxanthene_8 3, rugged] 2,(1Ή) ketone (75%), colorless solid: MS(ES+)m/ Z465.7 (M+1), 4667 (M+1). Example 4.118 1 -(2,1,3-benzothiadiazole_5-ylmethyl)_2 3_dihydrospiro[吱,[2,3 g][14]benzodioxanthene- 8,3'-吲哚]-2,(ιή)-ketone synthesis

Displacement of 2-(bromomethyl)tetrahydro-2-indole with 5-(indiylthio)-2,1,3-benzothiadiazole according to the procedure as described in Example 4, and with irrelevant changes味喃' and the use of 2,3-dihydrospiro [snolo[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2' (1Ή) - Ketone replacement of 5,6-dihydrospiro[benzo[i,2-b:5,4-b1]difuran-3,3'-啕哚]-2&quot;(1Ή)-鲷, obtained 1, -(2,1,3-benzothiadiazole_5_ylmethyl)_2,3_ a wind snail [吱°南和[2,3_和][1,4] benzodioxan _8,3'^5丨嗓]-2|(1'11)-ketone (80%) ' is a colorless solid: melting point ^9-1911; WNMRGOOMHz 'CDCla) •527· 143924-sp-2009l 127-3 C. 201020257 (5 8.04-7.90 (m, 2H), 7.63-7.55 (m, 1H), 7.22-7.15 (m, 2H), 7.08-7.00 (m, 1H), 6.86-6.79 (m, 1H), 6.53 (s, 1H), 6.26 (s, 1H), 5.22 (d, J = 15.9 Hz, 1H), 5.04 (d, J = 15.9 Hz, 1H), 4.97 (d, J = 9.0 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.24-4.10 (m, 4H); MS (ES+) m/z 443.8 (M + 1) 〇 Example 4.19 Γ-(1,3-benzopyrazole-2 -ylindolyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-啕] -Τ (1Ή) - one Synthesis of

Displacement of 2-(bromomethyl)tetrahydro-2-indole by 2-(bromomethyl)-l,3-benzoxazole according to the procedure as described in Example 4 and subject to insignificant changes And use 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3,_吲哚]-2'(ΓΗ)- Ketone replacement of 5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuranium]-2&quot;(1Ή)-ketone' to obtain ι'-(ι,3-benzophenone Pyrazole-2-ylmethyl)_2,3-dihydrospiro[&gt; husband and [2,3-g][l,4]benzodioxanene_8,3,_10; Ι_2'(ι'η)-ketone (77%) as colorless solid: m.p. 164-166°C; iHNMRGOOMHz 'CDCl.) &lt;5 8.04 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.54-7.46 (m, 1H), 7.43-7.35 (m, 1H), 7.24-7.17 (m, 2H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.97 ( d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.41 (s, 1H), 5.53 (d, J = 16.2 Hz, 1H), 5.24 (d, J = 16.2 Hz, 1H), 4.97 ( d, J = 9.0 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.24-4.11 (m, 4H); 13 C NMR (75 MHz, CDC13) δ 177.2, 165.9, 155.3, 152.9, 144.7 , 141.2, 138.3, 135.3, 132.1, 128.9, 126.3, 125.5, 124.0, 1 23.9, 123.2, 121.9, 120.8, 111.8, 143924-sp-20091127-3 • 528 - 201020257 109.2, 99.4, 64.5, 63.9, 58.0, 42, 6; MS (ES+) m/z 442.8 (Μ + 1). Example 4.120 Γ-[(1-Methyl-1 Η-benzimidazole_2-yl)methyl]_2,3_dihydrospiro[啥,[2,3-荩][1,4]benzoic Oxygen-based olefins _8,31_吲哚]_2, (1, _ _ 嗣 synthesis

φ In accordance with the procedure as described in Example 4, and with irrelevant changes, 2-(bromoindenyl)tetrahydro-substituted with 2-(indiyl)-1-mercapto-1H-benzimidazole 2H- shouting 'and using 2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene-8,3% 哚]-2' (1Ή )-keto-substituted 5,6-dihydrospiro[benzo[i,2-b: 5,4,7]didentate-3'3'-吲哚]-2Π(1Ή)-one, obtained ι' -[(ΐ-Methyl-1Η^andimidazolium-2-yl)indenyl]_ 2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene _8,3,_吲哚]-2'(1Ή)-_(20%), is a colorless solid: melting point &gt;24 (y&gt;c; iHNMR(3〇〇MHz, CDC13) δ 7.58-7.53 (m , 2H), 7.30-7.14 (m, 5H), 7.06-6.99 (m, 1H), 6.60 (s, ® 1H), 6.51 (s, 1H), 5.28 (ABq, 2H), 4.81 (d, J = 9.3 Hz, 1H), 4.71 (d, J = 9.3

Hz, 1H), 4.22-4.10 (m, 4H), 3.85 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 176.6, 154.5, 149.1, 144.1, 142.3, 141.7, 137.8, 136.1, 131.9, 128.5 , 123.3, 123.0, 122.1, 121.5, 121.4, 118.6, 112.0, 110.1, 109.7, 98.5, 79.3, 64.1, 63.6, 57.3, 37.1, 29.8; MS (ES+) m/z 440 Ό (M + 1). Example 4.121 Γ-{[2-(1-mercaptoethyl)-l,3-oxazole-4-yl]indolyl}-2,3-dihydrospiro[吱,[2,3-g Synthesis of [l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-_ 143924-sp-20091127-3 -529 - 201020257

Displacement of 2-(bromomethyl)tetrahydro-2H-pyranose using 4-(methylmethyl)-2-isopropylpyrazole according to the procedure as described in Example 4 and subject to insignificant changes And using 2,3-dihydrospiro[pfurano[2,3_g][i,4]benzodioxolene-8,3,_啕哚]-2'(ΓΗ)-one substitution 5 ,6-dihydrospiro[benzo[i,2_b : 5,4?']difuran-3,3,-4丨嗓]-2 (1H)-class' obtained Γ-{[2-(1-曱基ethyl)_ι,3_^ 〇圭_4_基]Methyl b 2,3_ Dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8 ,3·_峋哚]_2,g,H)__ (95%) ' is a colorless solid: melting point 6〇-63°C; 4 NMR C300 MHz, ΟΧ:13) δ 7.28-7.21 (m, 1Η), 7.16 (d, J = 7.4 Hz, 1H), 7.06-6.98 (m, 2H), 6.92 (s, 1H), 6.50 (s, 1H), 6.26 (s, 1H), 5.15 (d, J = 16.2 Hz , 1H), 4.95 (d, J = 16.2 Hz, 1H), 4.93 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.22-4.08 (m, 4H), 3.37 -3.22 (m, 1H), 1.39 (d, J = 6.9 Hz, 6H); 13 C NMR (75 MHz, CDC13) 5 178.5, 177.2, 155.2, 150.2, 144.6, 142.1, 138.3, 132.2, 128.8, 123.7, 123.4, 121.1, 114.1, 111.6, 109.7, 99.4, 80.1, 64.5, 63.9 , 58.1, 40.6, 33.3, 23.1 ; MS (ES+) m/z 434.9 (M + 1) ° Example 4·122 1'-(2,1,3-Benzoxadiazol-5-ylmethyl)- Synthesis of 2,3-dihydrospiro[2,3-phantom [1,4]benzodioxanthene-8,3'-(9)哚]-2\1Ή)-one

143924-sp-20091127-3 -530 201020257 Following the procedure as described in Example 4, and performing an insignificant change, using 5-(Moalylmethyl)-2,1'3-benzoxadiazole replacement 2_ (bromomethyl)tetrahydro-2H_pyran, and the use of 2,3-dihydrospiro[吱-benzodioxanthene-8,3·-吲哚]-2'(1Ή)-嗣Substitution of 5,6-dihydrospiro[benzo-like seven:5,4-7,]difuran-3,3W丨嗓]-2"(1Ή)-ketone-obtained benzoxadiazole-5-yl group Base) 2,3_-hydrogen snail [吱,[2,3-g][l,4]benzodioxanthene) _2,(1Ή)__ (44%) ' is a colorless solid: melting point 164_166i ; lHNMR(3()()MHz, eDa3) δ 7.86 (d, J = 9.3 Hz, 1H), 7.75 (s, 1H), 7.43-7.37 (m, 1H), 7.25-7.19 (m, ❺ 2H ), 7.08 (dd, J = 7.5, 7.5 Hz, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.23 (s, 1H), 5.13 (d, J = 16.2 Hz) , 1H), 4.95 (d, J = 9.0 Hz, 1H)S 4.94 (d, J = 16.2 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.24-4.10 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.7, 155.3, 149.0, 148.7, 144.8, 141.4, 139.7, 138.4, 132.0, 131.4, 129.0, 124.3, 124.0, 120.6, 117.8, 113.9, 111.4, 108 .8, 99.6, 80.1, 64.5, 63.9, 58.0, 44.0; MS (ES+) m/z 427.9 (M + 1). Example 4.123 @ 4-[(2·-keto-2,3-dihydrospiro[吱 并[2,3_g][1,4]benzodioxanthene _8,3,_ 嗓]-Γ(2Ή)-yl)methyl]hexahydropyridyl small carboxylic acid third- Synthesis of butyl ester

Displacement of 2-(Molylmethyl) with 4-(butylsulfonyloxyindenyl)hexahydropyridine carboxylic acid tert-butyl ester according to the procedure as described in Example 4 and subject to insignificant changes Tetrahydro 2 hydrazine-pyran, and the use of 2,3-dihydrospiro[吱, 143924-sp-20091127-3 -531 - 201020257 [2,31][1,4] benzodioxanthene- 8,3.5丨哚]-2'(1 ugly)-ketone replacement 5,6-dihydrospiro[benzo[1,2-b: 5,4-b.]difuran-3,3'-吲哚]-2&quot;(1Ή)-ketone to obtain 4-[(2·-keto-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxan) Benzene-8,3'-啕哚Η'(2Ή)-yl)indolyl] hexahydropyridine-1-carboxylic acid tert-butyl ester (99%) as colorless solid: 4 NMR (300 MHz, CDC13 &lt;5 7.34-7.26 (m,1Η), 7.14-7.19 (m, 1H), 7.08-7.01 (m, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.19 (s, 1H), 4.87 (d, J = 9.0 Hz, 1H), 4.62 (d, J = 9.0 Hz, 1H), 4.23-4.06 (m, 6H), 3.80-3.44 (m, 2H), 2.76 -2.59 (m, 2H), 2.11-1.93 (m, 1H), 1.74-1.60 (m, 2H), 1.45 (s, 9H), 1.37-1.20 (m, 2H). Example 4.124 1'-(Acridin-2-ylindenyl) snail [吱,[3,2-e][2,l,3]benzo”diazole-8,3'- 哚]]- Synthesis of 2'(1Ή)-ketone

Following the procedure as described in Example 4, and carrying out irrelevant changes, replacing 2-(bromomethyl)tetrahydro-2-indole with 2-(Moalylmethyl)pyridinidine, and using a snail And [3,2-e][2,l,3]benzox»diazole_8,3,_啕嗓]-2'(ΓΗ)-one replaces 5,6-dihydrospiro[benzo [i,2-b: 5,47']difuran-3,3,-吲哚]-2,,(1Ή)-one, obtained Γ-(bite-2-ylmethyl) snail [吱喃[3,2_e][2,i,3]benzoxadiazole_8,u 嗓]-2'(1Ή)-嗣(81%), as colorless solid: melting point 18〇_182〇c; iHNMR(3〇〇MHz, CDC13) ά 8.63-8.59 (m, 1Η), 7.84 (d, J = 9.6 Hz, 1H), 7.77-7.70 (m, 1H), 7.57 (d, J = 7.8 Hz, 1H ), 7.32 (d, J = 9.6 Hz, 1H), 7.28-7.16 (m, 3H), 7.04 (ddd, J = 7.5, 7.5, 0.9 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H) , 5.45 (d, J = 16.2 143924-sp-20091127-3 -532· 201020257

Hz, 1H), 5.28 (d, J = 9.6 Hz, 1H), 5.01 (d, J = 9.6 Hz, 1H), 4.92 (d, J = 16.2 Hz, 1H) ; 13 C NMR (75 MHz, CDC13) &lt;5 176.1, 163.0, 155.1, 149.4, 148.3, 144.9, 142.2, 137.3, 129.8, 129.7, 123.7, 123.67, 122.8, 121.9, 121.6, 119.4, 110.1, 107.0, 82.0, 57.4, 46.5; MS (ES+) m /z 371.0 (M + 1). Example 4.125 Γ-0»pyridin-3-ylindenyl) snail [Etho[3,2-New 2,1,3]Benzacoxadiazole-8,3," bow | 哚]-2' (1Ή)-ketone synthesis

Follow the procedure as described in Example 4, and perform irrelevant changes, using 3-(bromomethyl oxaridinium hydrobromide to replace 2-(bromomethyl)tetrahydro-2 oxime - snoring, and use Snail [吱,[3,2-e][2,l,3]benzoxadiazole-8,3'-throindole]-2·(1Ή)-one is substituted for 5,6-dihydrospiro [ Benzo[l,2-b:5,4-b.]difuran-3,3·-啕哚]-2Μ(1Ή)-one, Γ-(pyridin-3-ylindenyl) snail喃[3,2-e][2,l,3]benzoxadiazole-8,3,-吲哚]-2,(1Ή)-one (47%), as colorless solid: melting point 230- 232. WNMR (300 MHz, CDC13) δ 8.74 (s, 1H), 8.59 (d, J = 2.7 Hz, 1H), 7.88-7.82 (m, 2H), 7.39-7.16 (m, 4H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.80 (d, J = 7.8 Hz, 1H), 5.35-5.24 (m, 2H), 4.99 (d, J = 9.3 Hz, 1H), 4.84 (d, J = 15.9 Hz, 1H); 13C NMR (75 MHz, CDC13) δ 176.1, 162.9, 149.4, 148.8, 148.3, 144.8, 141.7, 135.1, 130.8, 129.8, 129.7, 123.9, 121.8, 119.4, 109.6, 106.9, 81.9 , 57.2, 42.0 ; MS (ES+) m/z 371.1 (M + 1) 〇 Example 4.126 6-Gas-Γ-(pyridin-2-ylindenyl)-2,3-dihydrospiro[吱吱[ 3,2-f][l,4]benzone 14 3924-sp-20091127-3 •533· 201020257

Synthesis of Oxygenene-9,3'-吲哚]-2,(i,h)-one

Following the procedure as described in Example 4, and carrying out irrelevant changes, 2-(bromo-mercaptohydronadine was substituted for 2_(bromoindenyl)tetrahydro-2H-pyran, and 6-gas-2 was used. ,3-dihydrospich-bromo-[Ye, 々] benzodioxanthene _9,3,(5) 哚]-2'(1Ή)-one, replacing 5,6-dihydrospiro[benzene And [i,2-b: 5,4,7,]difuran_3,3,5丨嗓]-2"(1Ή)-one, 6-yl-indole-2-ylindenyl -2,3-dihydrospiro[吱,[3,2-f][l,4]benzodioxanthene-9,3,-嘀哚]-2,(1Ή)-one ( 81%), colorless. Solid: melting point 197-199 ° C; WNMR (300 MHz, CDC13) (58.60 (d, J = 2.1

Hz, 1H), 7.60 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H), 7.32 (d, J = 7.5 Hz, 1H), 7.25-7.15 (m, 3H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 6.83 (d, J = 7.5 Hz, 1H), 6.79 (s, 1H), 5.35 (d, J = 16.2 Hz, 1H), 5.00 (d, J = 9.3 Hz, 1H), 4.89 (d, J = 16.2 Hz, 1H), 4.74 (d, J = 9.0 Hz, 1H), 4.16-3.86 (m, 4H); 13C NMR (75 MHz, CDC13) S 175.9, 155.8, 151.7, 149.5, 141.8 , 138.6, 138.3, 136.7, 130.9, 128.9, 123.6, 123.4, 122.6, 121.4, 118.2, 116.8, 109.4, 106.8, 81.7, 64.5, 63.8, 57.7, 46.3; MS (ES+) m/z 421.2 (M + 1) , 423.2 (M + 1). Example 4.127 1'-Azetidin-2-ylmethyl)-2,3-dihydrospiro[吱,[3,2-£][1,4]benzodioxene _9,3 '_哚哚]-2'(1Ή)-ketone synthesis 143924-SP-20091127-3 -534- 201020257 p

Following the procedure as described in Example 4, and carrying out irrelevant changes, 2-(bromomethyl) substituted with 2-pyridine (2-bromomethyl)tetrahydro-2h-pyran, and 2,3- Dihydrospiro[furo[3,2^14]benzodioxolene _9,3,_ 哚 哚]_ 2·(1Ή)-_substituted 5,6-dihydrospiro[benzo[1] , 2 7: 5, 4 VII.] 吱 吱 _3, 3, ten] _ φ 2" (1 Ή) ketone, obtain l'-K pyridine-2-ylmethyl)-2,3- two Hydrogen snail [吱mm[hmm] benzo-oxo sulphate-9X嗓]-2'(1Ή)-ketone (38%) as colorless solid: melting point 132-134 C ; 4 NMR (300 MHz, CDC13 5 8.60 (d, J = 1.2 Ηζ, 1 Η), 7.60 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H), 7.38-7.13 (m, 4H), 7.01 (dd, J = 7.2, 7.2 Hz, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 6.47 (d, J = 8.4 Hz, 1H), 5.38 (d, J = 16.2 Hz, 1H) , 4.96-4.83 (m, 2H), 4.65 (d, J = 8.7 Hz, 1H), 4.17-3.86 (m, 4H); 13C NMR (75 MHz, CDC13) δ 176.6, 156.0, 155.9, 149.4, 141.7, 139.6, 138.0, 136.7, 131.5, 128.6, 123.5, 123.2, 122.6, 121.4, φ 118.1, 115.7, 109.2, 102.4, 81.4, 64.5, 63.8, 57.2, 46.2 ; MS (ES+) m/z 387.2 (M + l) . Example 4.128 4-[(5,6-Difluoro-2'-oxaspiro[1-benzofuran-3,3'-throindole]-indole (2Ή)-yl)indolyl]hexahydropyridin-1 - Synthesis of carboxylic acid tert-butyl ester 143924-sp-20091127-3 -535- 201020257

Displacement of 2-(bromodecyl)tetrazide with 4 (p-benzenesulfonyloxymethyl)hexahydropyridine carboxylic acid tert-butyl ester according to the procedure as described in Example 4 and subject to insignificant changes Hydrogen 2H_ shouting, and using % difluorospirobenzofuran _3,3'^|嗓]-2'(ΓΗ)-鲷 to replace 5,6-dihydrospiro [benzo is called seven:5, 4 b,]difuran-3,3·-derivative]-2"(1,H)-ketone' gives 4_[(5,6-difluoro-2,_oxaspiro fl benzofuran_3,3 , _ 4哚Η'(2Ή)-yl) fluorenyl] hexahydropyridine carboxylic acid, third butyl (57%), colorless solid: 4 NMR (300 MHz, CDC13) 6 7.34 _, J = 9.0 , 7.6, 1.5 Ηζ, 1Η), 7.16-7.06 (m, 2H), 6.92 (d, J = 7.8 Hz, 1H), 6.78 (dd, J = 10.3, 6.3 Hz, 1H), 6.49 (dd, J = 10.3, 6.3 Hz, 1H), 4.95 (d, J = 9.0 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.13 (br s, 2H), 3.74-3.56 (m, 2H), 2.69 (t, J = 12.4 Hz, 2H), 2.07-1.96 (m, 1H), 1.68-1.63 (m, 2H), 1.45 (s, 9H), 1.32-1.26 (m, 2H) ; MS (ES+) m /z 493.3 (M +23). Example 4.129 ❹ 1-[(2R)-E9hydrofuran-2-ylmethyl]_5,,6'j',8,-tetrahydrospiro(tetra)pyrene-3,3, _Naphtho[2,3-b]furan]-2 Synthesis of (1H)-ketone

Displacement of 2-(bromomethyl) 143924-sp with (R)-(tetrahydrofuran-2-yl) decyl 4-methylbenzenesulfonate according to the procedure described in Example 4, and with irrelevant changes -20091127-3 -536- 201020257 Tetrahydro-211-pyran, and using 5',6|,7',8|-tetrahydrospiro|&gt;?丨哚-3,3^荇[2,3 VII]furan]-2(1H)-one replaces 5,6-dihydrospiro[benzo[l,2-b:5,4-b1]difuran-3,3·-啕哚]-2" ( 1-Ή)-ketone, 1-[(2R)-tetrahydrofuran-2-ylmethyl]-5Ά,7·,8'-tetrahydrospiro-3,3'-indole[2,3-b Furan]-2(1Η)-one (80%) as a colorless solid: m.p. 139-141 〇C; lH NMR (300 MHz, CDC13) &lt;5 7.32-7.27 (m, 1H), 7.15-7.01 ( m, 3H), 6.66 (s, 1H), 6.41 (s, 1H), 4.88 (dd, J = 8.9, 0.9 Hz, 1H), 4.63 (dd, J = 8.9, 2.5 Hz, 1H), 4.32-4.24 (m, 1H), 4.00-3.69 (m, 4H), 2.75-2.71 (m, 2H), 2.54 (br s, 2H), 2.10-1.86 (m, 3H), 1.78-1.69 (m, 5H); 13 C NMR (75 MHz, © CDC13) δ 178.0, 158.6, 142.9, 138.8, 132.4, 130.0, 128.6, 126.5, 123.6, 123.4, 123.2, 110.1, 109.5, 79.7, 76.9, 68.2, 57.9, 44.6, 29.9, 29.2 , 29.0, 25.6, 23 .2, 23.0 ; MS (ES+) m/z 375.9 (M + 1). Example 4.130 Γ-0 to bite-2-ylmethyl) snail [pf- s[2,3_g] sucralin _8, Synthesis of 3l吲哚]_2, (ι·η)_嗣

Following the procedure as described in Example 4, and carrying out an insignificant change, the 2-(bromomethyl)acridine hydrobromide was used to replace the 2(bromomethyl)tetrahydro----- - snail [吱,[2,3_g&gt; quinoxaline _8,3,_dihydro(9)哚]_2, ketone replaces 5,6-- snail [benzo[1,2 seven:5,4 seven ']difuran-3,3,5|哚]-2&quot;(1Ή)-ketone, obtained 1 - (bite-2-ylmethyl) snail [唉 并[2,3 Miao quinoxaline _ 8,3,(五)哚]Minyang ketone (93%), light orange solid: melting point 232_2 building; i η 143924-sp-20091127-3 •537- 201020257 CDC13) δ 8.64 (m, 1H), 8.59 (d, J = 1.5 Hz, 1H), 8.44 (d, J = 1.5 Hz, 1H), 8.05 (d, J = 9.3 Hz, 1H), 7.83 (d, J = 8.1 Hz, 1H), 7.77-7.67 (m, 1H), 7.56 (d, J = 9.0 Hz, 1H), 7.28-7.17 (m, 2H), 7.10 (d, J = 7.2 Hz, 1H), 6.96 (t, J = 7.5 Hz, 1H) , 6.84 (d, J = 7.8 Hz, 1H), 5.56 (d, J = 16.5 Hz, 1H), 5.25 (d, J = 9.0 Hz, 1H), 4.97 (d, J = 9.0 Hz, 1H), 4.91 (d, J = 16.5 Hz, 1H); 13 C NMR (75 MHz, CDC13) δ 177.2, 162.5, 155.9, 149.4, 144.9, 142.3, 142.1, 139.8, 139.8, 136.9, 132.6, 132.4, 128.8, 123.3, 123 .2, 122.6, 121.9, 121.4, 116.6, 109.6, 82.6, 57.7, 46.5; MS (ES+) m/z 381.2 (M + 1). Example 5 Γ-[(2-Methoxypyrimidin-5-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3, Synthesis of 3'-吲哚]-2·(1Ή)-ketone

'at 5,6-dihydrospiro[benzo[^7:5,4-b']difuran-3,3,-(9)哚]-2'(1Ή)-one (0.28 g, at ambient temperature) 1.0 mmol of cesium carbonate (23 g, 7 rpm) was added to a stirred solution of anhydrous N N dimethylformamide (6 mL). The mixture was stirred at ambient temperature for 3 minutes and 5 (v-methyl) 2 methoxypyrimidine (0.34 g, 2.1 mM) in anhydrous N,N-dimercaptoacetamide (3 ml). Moore). The mixture was stirred at ambient temperature for 16 hours and additional carbonic acid (0. 68 g, 21 mmol) and &lt;5&quot;&quot; The mixture was stirred at ambient temperature for 64 hours. Water (60 ml) was added and the mixture was extracted with ethyl acetate (EtOAc). The combined organic solutions were washed with brine (1 mL), dried EtOAc EtOAc EtOAc EtOAc EtOAc. The residue was purified by column chromatography (hexane/ethyl acetate 1:1) to give bis-[(2-methoxypyrimidine_5_

Methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2·(1,Η)- Ketone (0.29 g '73%) as a colorless solid: m.p. (: ; iHNMRQOO MHz, CDC13) δ 8.57 (s, 2H), 7.30-7.23 (m, 1H), 7.22-7.17 (m, 1H), 7.11- 7.04 (m, 1H), 6.86-6.81 (m, 1H ), 6.44-6.41 (m, 2H), 4.89 (ABq, 2H), 4.81 (ABq, 2H), 4.59-4.50 (m, 2H), 4.01 (s, 3H), 3.10-2.90 (m, 2H); 13C NMR (75 MHz, CDCI3) 5 177.9, 165.4, 161.9, 161.3, 158.8, 141.1, 132.7, 128.8, ® 124.3, 123.9, 122.8, 120.1, 119.7, 118.7, 108.5, 93.3, 80.5, 72.4, 57.6, 55.1, 38.8, 29.0; MS (ES+) m/z 402.1 (M + 1). Example 5.1 7'-Gasyl-indole-((5-(trifluoromethyl)c-butyl-2-yl)methyl)-5,6-dihydro-2H-spiro[benzofuran[6,5 Synthesis of -b]pyran-3,3,-dihydroanthracene-2,-one

According to the procedure as described in Example 5, and irrelevant changes were made, 7·-gas-based-5,6-dihydrospiro[benzo-like 7:5,4-b,]difuran-3,3 was used. ,-啕哚]-2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[[7:5,4-7,]difuran_3,3,-吲哚]-2' (1Ή )-ketone' and the use of 2-(fillyl fluorenyl)_5_(trifluoromethyl) succinyl to replace 5_(gas thiol)-2-methoxypyridine to obtain 7, _ gas group_1L (( 5_(Trifluoromethyl)-n-butyl-2-yl)methyl)-5,6-dihydro-2H-spiro[benzofuran [6,5 失 _ _3,3,_ dihydroanthracene ]_2, ketone (30%), as a colorless solid: m.p. 〇 (ether 1H (3〇〇MHz, DMSO-d6) δ 7.34-7.31 (m, 1Η), 7.21-7.16 (m, 2H), 7.10-7.05 (m, 1H), 143924-sp-20091127-3 if E -539- 201020257 6.67-6.65 (m, 1H), 6.49 (s, 1H), 6.43 (s, 1H), 5.34 (s, 2H), 4.85 (d, J = 9.6 Hz, 1H), 4.74 (d , J = 9.6 Hz, 1H), 4.57-4.48 (m, 2H), 2.94 (t, J = 3.0 Hz, 2H); 13C NMR (75 MHz, DMSO-dg) &lt;5 177.4, 161.2, 160.4, 154.1 , 139.4, 138.9, 137.2, 135.4, 130.5, 124.6, 122.8, 120.6, 120.1, 119.9, 118.7, 117.1, 114.3, 114.2, 108.7, 92.4, 79.8, 72.0, 56.6, 28.1. Example 5.2 (3R)-r-( 3-methylbutyl)_5,6-dihydrospiro- i; benzo-like -7·5,4-7;|difuran_3,κ 哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 5, and irrelevant changes were made, (311)-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3 was used. , 3,-(9)哚]-2'(ΓΗ)-keto-substituted 5,6-dihydrospiro[benzopyrene:5,4-b,]difuran-3,3,-rhodium]-2, (1Ή)-ketone' and the substitution of 5-(carbomethyl)-2-oxooxypyrimidine with 1-bromo-3-methylbutane to obtain (3R)-l'-(3-methyl Butyl)_5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-indole]-2'(1Ή)-one (86%) , a colorless solid: melting point 86-87. (: (ether)·' 1H NMR (300 MHz, CDC13) &lt;5 7.33-7.26 (m,1Η), 7.17 (d, J = 7.4 Ηζ, 1H), 7.07-7.02 (m, 1H), 6.90 ( d, J = 7.8 Hz, 1H), 6.45 (s, 1H), 6.41 (s, 1H), 4.92 (d, J = 8.9 Hz, 1H), 4.66 (d, J = 8.9 Hz, 1H), 4.52 ( t, J = 8.6 Hz, 2H), 3.88-3.65 (m, 2H), 3.02-3.96 (m, 2H), 1.74-1.58 (m, 3H), 1.00 (d, J = 6.3 Hz, 6H) ; 13C NMR (75 MHz, CDC13) δ 177.5, 161.7, 161.2, 142.3, 133.1, 128.6, 123.8, 123.0, 120.3, 119.8, 118.7, 108.4, 93.1, 80.5, 72.3, 57.6, 38.7, 143924-sp-20091127-3 - 540- 201020257 36.1, 29.0, 26,0, 22.5, 22.4 ; MS (ES+) m/z 349.9 (Μ + 1). Example 5.3 (3R)-1·-pentyl-5,6-dihydrospiro[benzene And [i,2-b: 5,4-b,]difuran-3,3,"丨哚丨哚]-2'(1Ή)-ketone synthesis

❹ (3 ft)-5,6-dihydrospiro[benzo[i,2_b : 5,4_b,]difuran-3,3 was used according to the procedure described in Example 5, and irrelevant changes were applied. ,-吲哚]-2'(1Ή)-ketone-substituted 5,6-dihydrospiro[benzopyrene-7:5,4-7']difuran-3,3,-W哚 steel, and 1-bromide Substituting 5-(alkylfluorenyl)-2-nonyloxypyrimidine for pentane to obtain (3R)-1'-pentyl-5,6-dihydrospiro[{,2-b: 5, 4-b,]difuran-3,3'-indole]-2'(1Ή)-one (78%) as colorless solid: m.p., i28-129t (diethyl ether); lH NMR (300 MHz, CDC13) &lt;;5 7.33-7.26 (m, 1H), 7.17 (d, J = 7.1 Hz, 1H), 7.07-7.02 (m, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H) , 6.41 (s, 1H), 4.92 ® (d, J = 8.9 Hz, 1H), 4.67 (d, J = 8.9 Hz, 1H), 8.64 (t, J = 4.5 Hz, 2H), 3.87-3.63 (m , 2H), 2.99 (t, J = 4.5 Hz, 2H), 1.79-1.69 (m, 2H), 1.40-1.35 (m, 4H), 0.94-0.89 (m, 3H); 13C NMR (75 MHz, CDC13 ) δ 177.5, 161.6, 161.2, 142.4, 133.0, 128.6, 123.8, 123.0, 120.3, 119.7, 118.7, 108.4, 93.1, 80.5, 723, 57.6, 40, 3, 29.0, 27.1, 22.3, 13.9; MS (ES+) m/z 349.9 (M + 1). Example 5.4 (31〇-1&gt;bipyridin-2-ylindenyl)-5,6-dihydrospiro[benzo[1,2-7:5,4-7']difuran-3,3,-啕哚]-Τ(ΓΗ)-ketone synthesis 143924-SD-20091127-3 •541- 201020257

According to the procedure as described in Example 5, and irrelevant changes were made, using (3R)-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3 ,3'-吲哚]-2,(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-rhodium ]-2,(1,Η)-one, and 5-(chloromethyl)_2~methoxypyrimidine was replaced with (2-bromomethyl)pyridine hydrobromide to obtain (3R)-r- (pyridin-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2_b : 5,4_b']difuran-3,3,-τ·5丨哚]-πι'Η)- Ketone (77%), colorless solid: mp 154-156 ° C (ethyl ether); iHNMRpOOMHiDMSO-dd 5 8.53-8.51 (m, 1H), 7.82-7.77 (m, 1H), 7.38-7.13 (m, 4H ), 7.05-6.99 (m, 1H), 6.98-6.92 (m, 1H), 6.61 (s, 1H), 6.42 (s, 1H), 5.10 (d, J = 16.4 Hz, 1H), 5.00 (d, J = 16.4 Hz, 1H), 4.86 (d, J = 9.3 Hz, 1H), 4.75 (d, J = 9.3 Hz, 1H), 4.49 (t, J = 8.7 Hz, 2H), 2.98 (t, J = 8.7 Hz, 2H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.0,

161.0, 160.4, 155.2, 149.2, 142.4, 137.0, 132.2, 128.5, 123.4, 122.8, 122.6' 121.5, 120.6, 119.7, 119.2, 109.2, 92.3, 79.7, 72.0, 56.8, 44.7, 28.2 ; MS (ES+)m/ z 371.0 (M+l) 实例 Example 5.5 (3R)-r-{[5-glmethyl&gt; furan-2_yl] fluorenyl} 5 6 dihydrospiro [benzo[[7:5, Synthesis of 4-b']difuran-3,3,-吲哚]-2·(ΓΗ&gt; ketone

According to the procedure as described in Example 5, and the insignificant change was performed 143924-sp-20091127-3 -542- 201020257 using (3R)-5,6-dihydrospiro[benzo[l,2-b:5 , 4-b']difuran-3,3'-(9)哚]-2·(1Ή)-one substituted 5,6-dihydrospiro[benzo[l,2-b : 5,4-b·] Difuran-3,3W丨哚W(l'H)-ketone' and 5-(Chloroindenyl)-2-methoxyl substitution with 2-(bromomethyl)-5-(trifluoromethyl)furan Pyrimidine's (3R)-r-{[5-(trifluoromethyl)furan-2-yl]indolyl}-5,6-dihydrospiro[benzo[l,2-b: 5,4 -b']difuran-3,3,-anthracene-2·(1Ή)-one (83%) as colorless solid: mp. 68-70°C (diethyl ether); 4 NMR (300 MHz, CDC13) (5 Ί32-1.26 (m, 1H), 7.20 (d, J = 7.4 Hz, 1H), 7.10-7.05 (m, 1H), 6.98 (d, J = 7.8 Hz, 1H), 6.75-6.74 (m, 1H), 6.45 (s, 1H), 6.42 (s, 2H), 5.12 (d, J = 16.2 ® Hz, 1H), 4.96 (d, J = 9.0 Hz, 1H), 4.85 (d, J = 16.2 Hz , 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.54 (t, J = 8.6 Hz, 2H), 3.07-2.90 (m, 2H) ; 13 C NMR (75 MHz, CDCI3) δ 177.4, 161.8 , 161.1, 151.9, 141.9, 141.2, 132.5, 128.8, 123.9, 123.7, 120.5, 120.0 (2C), 118.7, 112 .6, 112.5, 109.2, 108.7, 93.1, 80.3, 72.3, 57.6, 36.8, 28.9, MS (ES+) m/z 427.9 + 1). Example 5.6 (3S)-1·-(10)biti-2-ylmethyl)_5 6_dihydrospiro[benzo[12:^^7-furan from

Synthesis of 吲哚]-2'(1Ή)-ketone

According to the procedure as described in Example 5, and carrying out irrelevant changes, use (3S)·5,6-dihydrospiro[benzo(10):5 state scorpion _3,3ι·10 illusion_2. Ketone replacement 5,6-hydrogen snail [benzo[U b : 5'4 b,] dim m ten] 2, (called 嗣, and use (2 ~ filling I methyl) gt; Salt substitution 5-(methyl-methyl methoxypyrimidine' to obtain (3S)-1L (pyridin-2-ylindenyl)5,6-dihydrospiro[:and- 143924-sp-20091127-3 r. -543- 201020257 [l,2-b: 5,4-b·]difuran-3,3'-indole]-2·(1Ή)-one (77%) as colorless solid: mp 154-156 °C (diethyl ether); m.p. 84-85°C (diethyl ether); 1H NMR (300 ΜΗζ, DMSO-de) δ 8.53-8.51 (m, 1 Η), 7.82-7.77 (m, 1H), 7.38-7.13 (m , 4H), 7.05-6.99 (m, 1H), 6.98-6.92 (m, 1H), 6.61 (s, 1H), 6.42 (s, 1H), 5.10 (d, J = 16.4 Hz, 1H), 5.00 ( d, J = 16.4 Hz, 1H), 4.86 (d, J = 9.3 Hz, 1H), 4.75 (d, J = 9.3 Hz, 1H), 4.49 (t, J = 8.7 Hz, 2H), 2.98 (t, J = 8.7 Hz, 2H); 13 C NMR (75 MHz, DMSO-d6) 5 177.0, 161.0, 160.4, 155.2, 149.2, 142.4, 137.0, 132.2, 128.5, 123.4, 122.8, 122.6, 121.5, 120.6, 119.7, 119.2, 109.2, 92.3, 79.7, 72.0, 56.8, 44.7, 28.2; MS (ES+) m/z 371.0 (M + 1). Example 5.7 (3 Magic_1'7-5-(trifluoromethyl)pyran-2 -yl]fluorenyl}-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-啕哚]-2'(1Ή)-one Synthesis

According to the procedure as described in Example 5, and carrying out irrelevant changes, use (38)-5,6-dihydrospiro[benzo[i,2_b:5,4,7], two ρ 失南-3 ,3,- 十朵]-2,(1Ή)-❹ 嗣Substitution of 5,6-dihydrospiro[Benzo[l,2-b: 5,4-7,]difuran-3,3,-called 丨哚]-2'(1Ή)- Brewing I' and using 2-(bromodecyl)_5_(trifluoromethyl)pyrene to replace 5_(gas-based fluorenyl)_ 2-methoxy mouth bite' π). ,7-5-(trifluoromethyl)furan-2-yl]methyl} 5,6-azaspiro[benzo[l,2-b:5,4-b,]difuran-3,3,-啕哚] ΑΙΉ)-ketone (83%) as colorless solid: m.p. 64-65 ° C (diethyl ether); 4 NMR (300 MHz, CDC13) (5 7.32-7.26 (m, 1H), 7.20 (d, J = 7.4 Hz, 1H), 7.10-7.05 (m, 1H), 6.98 (d, J = 7.8 Hz, 1H), 6.75-6.74 (m, 1H), 6.45 (s, 1H), 6.42 (s, 2H), 5.12 (d, J = 16.2 143924-SP-20091127-3 -544· 201020257

Hz, 1H), 4.96 (d, J = 9.0 Hz, 1H), 4.85 (d, J = 16.2 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H), 4.54 (t, J = 8.6 Hz, 2H), 3.07-2.90 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 177.4, 161.8, 161.1, 151.9, 141.9, 141.2, 132.5, 128.8, 123.9, 123.7, 120.5, 120.0 (2C), 118.7 , 112.6, 112.5, 109.2, 108.7, 93.1, 80.3, 72.3, 57.6, 36.8, 28.9; MS (ES+) m/z 427.9 (M + 1). Example 5.8 3-Methyl-1 '-{[5-(Trifluoromethyl)pyran-2-yl]methyl}spiro[吱,[2,3-f][l,3]benzoindole Synthesis of azole-7,3'-,5丨哚]-2,2·(1Ή,3Η)-dione

According to the procedure as described in Example 5, and irrelevant changes were made, 3-mercaptospiro[pf-pyrano[2,3-f][l,3]benzoxazole-7,3'-吲哚]-2,2·(1Ή,3Η)-dione replacement of 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3·-啕哚]-2·(1Ή)-ketone' and 5-(chloromethyl)-• 2-methoxypyrimidine using 2-(bromomethyl)-5-(trifluoromethyl)anthracene, 3-(Indolyl-indole-{[5-(trifluoromethyl)furan-2-yl]indolyl} spiro[furo[2,3-f][l,3]benzoxazole-7, 3·-吲哚]-2,2·(1Ή,3Η)-dione (59%), colorless solid: mp 198-199°C (diethyl ether); 1H NMR (300 ΜΗζ, DMSO-d6) δ 7.37 -7.30 (m, 1Η), 7.23-7.18 (m, 3H), 7.12-7.03 (m, 2H), 6.77 (s, 1H), 6.56 (s, 1H), 5.17-4.99 (m, 2H), 4.91 -4.75 (m, 2H), 3.31 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6) δ 176.2, 156.8, 154.3, 152.9, 141.5, 136.1, 132.9, 131.4, 128.9, 123.6, 123.3, 121.5 , 114.0 (2C), 109.8, 109.2, 104.2, 92.4, 79.3, 57.2, 36.4, 28.1; MS (ES+) m/z 456.4 (M+l). Example 5.9 143924-sp-20091127-3 -545· 201020257 1'-{[6-(III|L曱-based alkalidine-2-yl]methyl}_2 3_dihydrospiro [biting and arranging, 4 Synthesis of benzodioxanthene-8,3,-吲哚]-2,(1Ή)-one

2,3-Dihydrospiro[吱,[2,3_§][1,4]benzodioxene _8,3,啕哚]_ 2(1 H)-one (0.41 g' 1.4 millimolar), cesium carbonate (1.1 g, 丄 5 mmol), Lu 2-(chlorobenzyl)-6-(trifluoromethyl)acridine (0 33 g, i 7 mmol) An uneven mixture of N,N-dimethylformamide (10 ml) was stirred at ambient temperature for 16 hours. The mixture was diluted with water (100 mL) and ethyl acetate (1 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×EtOAc). The combined organic layers were washed with brine (100 mL), dried over anhydrous magnesium sulfate, filtered, and evaporated. The residue was purified by column chromatography and eluted with a gradient of 25% to 35% of ethyl acetate 6 to give 1'_丨[6_(trifluoromethyl)p ratio bite-2- Methyl}-2,3-hydrogen snail [p-chewing [2,3-g][l,4]benzodioxanthene _ -8,3'-p5|p]- 2'(1Ή)-class (0.44 g '70%), colorless solid: melting point 195-196 °C &gt; NMR (300 MHz, DMSO-dg) δ 8.15-8.07 (m, 1H), 7.85-7.79 ( m, 1H), 7.75-7.70 (m, 1H), 7.28-7.15 (m, 2H), 7.07-7.00 (m, 1H), 6.97-6.91 (m, 1H), 6.52 (s, 1H), 6.29 ( s, 1H), 5.16 (ABq, J = 42.6, 16.9 Hz, 2H), 4.75 (ABq, J = 37.3, 9.3 Hz, 2H), 4.22-4.08 (m, 4H) ; 13 C NMR (300 MHz, DMSO -d6) δ 176.8, 156.5, 154.6, 146.0 (q, JC.F = 33.7 Hz), 144.1, 142.3, 139.4, 137.8, 131.7, 128.6, 125.4, 123.5, 123.0, 121.4 (q, JC.F= 272.7 Hz ), 121.1, 119.5 143924-sp-20091127-3 •546· 201020257 (m),111.4, 109.1,98.6, 79.5, 64.1,63.5, 57.2, 44.2 ; MS (ES+) m/z 455.0 (Μ + 1) o Example 5.10 Γ-{[2-(Trifluoromethyl)P-pyridyl_3_yl]indenyl}_2,3_dihydrospiro[吱,[2,3_g][i,4] benzodioxine Lumene-8,3峋哚-2Χ1Ή)-ketone synthesis

Inconsistent changes were made according to the procedure described in Example 5.9, using 3-(methylmethyl)-2-(trifluoromethylidene) to displace 2-(azepine)-6-(trifluoro) Methyl acridine, Γ-{[2-(trifluoromethylacridin-3-yl)indolyl}-2,3-dihydrospich-[2,3-g][l,4 Benzodioxanthene-8,3'-,5丨哚]-2·(1Ή)-one (63%), as a colorless solid^^aaigJStrC^HNMRpOOMHz'DMSO-c^^S/yO- 8.65 (m,1H), 7.77-7.66 (m,2H),7.33-7.21 (m,2H),7.13-7.05 (13⁄4 1H), 6.90-10 6.83 (m, 1H), 6.52 (s, 1H), 6.37 (s, 1H), 5.14 (s, 2H), 4.78 (ABq, J = 42.3, 9.4

Hz, 2H), 4.23-4.07 (m, 4H) ; 13C NMR (300 MHz, DMSO-d6) δ 177.0, 154.7, 147,9, 144.2, 143.4 (q, Jc-F = 33.3 Hz), 142.0, 137 , 8, 136.3, 131.7, 130.8, 128.9, 127.7, 123.8, 123.3, 122.1 (q, JC_F = 275, 6 Hz), 120, 9, 111.6, 109.0, 98.7, 79.6, 64, 2, 63.5, 57.2, 48.5 MS (ES+) m/z 455.0 (M + l). Example 5.11 Γ-{[3-(Trifluoromethylidene-turmeric-2-yl]methyl}-2,3-dihydrospiro[, succinyl[2,3-g][l,4] benzodiazepine Synthesis of oxetene-8,3'-吲哚]-2'(1Ή)-one 143924-sp-20091127-3 .547- 201020257

Inconsistent changes were made according to the procedure described in Example 5.9, using 2-(bromomethyl)-3-(trimethyl)pyridine instead of 2 (chloroindenyl) 6 (trifluoromethyl) ) bite 'obtained 1'-{[3-(trifluoromethyl)[2]3-dihydrospiro[2,3-g][l,4] Stupid and diterpene terpene _8,3,_ρ?丨哚]_2, (1Ή)__ (72%), as a colorless solid: melting point 230-232. (: ; hNMR (300MHz, CDC13) (5 8.69- 8.66 (m, 1H), 8.60-8.57 (m, 1H), 7.23-7.15 (m, 2H), 7.08-7.01 (m, 1H)# 6.63-6.58 (m, 1H), 6.52 (s, 1H), 6.51 (s, 1H), 5.33 (ABq, J = 79.0, 17.6 Hz, 2H), 4.85 (ABq, J = 75.4, 8.9 Hz, 2H), 4.23-4.11 (m, 4H) ; 13C NMR (300 MHz, CDC13) δ 178.1, 155.1, 148.9, 146.8, 144.6, 142.1, 141.8, 141.7 (q, JC.F = 36.1 Hz), 138.2, 132.6, 128.7, 124.0, 123.6, 121.6 (q, JC-F = 273.4 Hz) , 121.2, 112.2, 108.2, 99.2, 80.0, 64.5, 63.9, 58.1, 41.2 (q, JC-F = 3.9 Hz); MS (ES+) m/z 455.9 (M + 1). Example 5.12 1'-{[ 4-(Trifluoromethylidin-3-yl)methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8 ,3'-吲哚]-2'(1 Ή)-ketone synthesis

143924.SP-20091127-3 • 548- 201020257 Following an insignificant change according to the procedure described in Example 5.9, using 3-(a gas-based fluorenyl)-4-(trifluoromethylsulfanyl hydrochloride) 3_(Chloromethyl 2-(trifluoromethylcyclohexane) obtains 1'-{[4-(trifluoromethylcycloazinyl)methyl b 2,3_dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene _8,3Lp? Budu]_2,(1Ή). (51%), colorless solid: melting point 131-132 ° C; iHNMRGOOMHz 'CDCl〗 ) δ 8.78-8.72 (m, 1H), 8.51 (s, 1H), 7.64-7.60 (m, 1H), 7.25-7.18 (m, 2H), 7.12-7.05 (m, 1H), 6.65-6.60 (m , 1H), 6.53 (s, 1H), 6.32 (s, 1H), 5.32-5.11 (m, 2H), 4.84 (ABq, J = 78.9, 8.9 Hz, 2H), 4.24-4.10 (m, 4H); 13C NMR © (300 MHz, CDC13) δ 177.9, 155.3, 149.9, 148.9, 144.8, 141.3, 138.4, 135.8 (q, JC-f= 32.8 Hz), 132.0, 129.1, 128.1, 124.3, 124.1, 123.0 (q, JC-F= 275.0

Hz), 120.4, 119.6 (10), 111.6, 108.8, 99.5, 80.2, 64.5, 63.9, 58.1, 38.8 (4); MS (ES+) m/z 455.0 (Μ + 1) 〇 Example 5.13 14 (6-Chlorobite bite - 2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3·-啕哚]-2· (1Ή)-ketone synthesis

According to the procedure as described in Example 5.9, an insignificant change was made using 2-methyl-6-(chloromethylcyclopyridine hydrochloride to replace 3_(carbomethyl)_2_(trifluoromethyl: Kt) Acridine, obtaining 14(6-aphthyridin-2-yl)methyl]·2,3-dihydrospiro [bito[2'3-g][l,4] benzodioxanthene- 8,3,_吲哚]_2ι(1Ή)__ (9〇%), as colorless solid: mp 181-182. (: 4 NMR (300 MHz, CDC13) &lt;5 7.67-7.59 (m, 143924- Sp-20091127-3 -549- 201020257 1H), 7.28-7.22 (m, 2H), 7.22-7.13 (m, 2H), 7.08-7.02 (m, 1H), 6.90-6.84 (m, 1H), 6.52 ( s, 1H), 6.32 (s, 1H), 5.23-5.14 (m, 1H), 4.98-4.89 (m, 2H), 4.70-4.65 (m, 1H), 4.24-4.09 (m, 4H) ; 13C NMR (300 MHz, CDC13) δ 177.5, 156.4, 155.2, 151.2, 144.6, 141.7, 139.7, 138.3, 132.1, 128.9, 123.9, 123.7, 123.4, 120.8, 119.9, 111.6, 109.3, 99.4, 80.1, 64.5, 63.9, 58.1 , 45.4; MS (ES+) m/z 420.7 (M + 1), 422.7 (M + 1) 〇 Example 5.14 Γ-[(2-曱-oxypyrimidin-5-yl)indolyl]-2,3-di Synthesis of hydrogen snail [bito-and-[2,3-g][l,4]benzodioxanthene-8,3'-throindole]-2'(1Ή)-one

According to the procedure as described in Example 5.9, an insignificant change was made using 5-(chloromethyl)-2-oxooxypyridinium hydrochloride to replace 3-(glycosyl)-2-(trifluoromethyl) Base &gt; pyridine, 1'-[(2-oxixypyrimidin-5-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4] Benzodioxantemene _8,3,_吲哚]-2,(1Ή)-one (47%), colorless solid: mp 248-249 ° C; iHNMRGOOMHz 'DMSO-dg) occupies 8.64 (s , 2H), 7.34-7.27 (m, 1H), 7.21-7.14 (m, 2H), 7.08-7.01 (m, 1H), 6.51 (s, 1H), 6.10 (s, 1H), 4.98-4.85 (m , 2H), 4.73 (ABq, J = 49.9, 9.4 Hz, 2H), 4.21-4.06 (m, 4H), 3.89 (s, 3H) ; 13 C NMR (300 MHz, CDC13) δ 176.8, 164.6, 158.9, 154.6, 144.1, 141.6, 137.7, 131.8, 128.7, 123.6, 123.5, 123.1, 121.0, 110.9, 109.2, 98.7, 79.3, 64.1, 63.5, 57.1, 54.6, 38.0; MS (ES+) m/z 418.2 (M + 1 ). Example 5.15 143924-sp-20091127-3 • 550· 201020257 1 -[(6-methoxyu-biti-3-yl)indenyl]_2,3-dihydrospiro[吱,[2,3-g Synthesis of [l,4]benzoxantheneene-8,3'-吲哚]-2'(1Ή)-one

Inconsistent changes were made according to the procedure described in Example 5.9 'Replacement of 3-(chloromethyl)-2-(3) with 5-(chloromethyl)-2-methoxypyridine hydrochloride Based on hydrazine, 1 L of [(6-methoxypyridin-3-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzoic acid was obtained. Oxygen olefins _8,3, _ 哚 哚]_2, (1 Ή), (34%), as a colorless solid: melting point 161-162 ° C; 4 NMR (300 MHz, DMSO-d6) 5 8.26-8.22 ( m, 1H), 7.69-7.63 (m, 1H), 7.32-7.25 (m, 1H), 7.19-7.08 (m, 2H), 7.07-7.00 (m, 1H), 6.84-6.79 (m, 1H), 6.52 (s, 1H), 6.05 (s, 1H), 4.91-4.86 (m, 2H), 4.73 (ABq, J = 42.8, 9.4 Hz, 2H), 4.22-4.06 (m, 4H), 3.82 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 176.7, 163.0, 154.6, 145.9, 144.1, 141.8, φ 138.5, 137.7, 131.7, 128.7, 125.0, 123.6, 123.1, 121.1, 110.8, 110.7, 109.3, 98.8 , 79.3, 64.1, 63·5, 57.2, 53.1; MS (ES+) m/z 416.9 (M+l). Example 5.16 (8S)-r-(pyrino-2-ylmethyl)-2,3- Synthesis of dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3'-吲哚]_2,(1,Η)-one

According to the procedure as described in Example 5.9, an insignificant change was made to make 143924-sp-20091127-3 •551 - 201020257 a 2-(chloro-based sulfhydryl-based wind-fighting replacement of 3_(gas-based thiol)_2-(three Fluoromethyl&gt; pyridine, and (8S)-2,3-dihydrospiro[pf- oxa- gamma KM]benzodioxene-8,3WI 哚]-2\1Ή)-ketone replacement 2 ,3-dihydrospiro[?,[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one, obtained (π )-!,-(pyroxy-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3 ,-吲哚]_2,(1Ή)-ketone (62%), as colorless solid: mp 216-218 ° C; 4 NMR (300 MHz, CDC13) (5 8.65-8.62 (m, 1H), 8.58-8.50 (m, 2H), 7.27-7.15 (m, 2H), 7.09-7.01 (m, 1H), 6.91-6.85 (m, 1H), 6.51 (s, 1H), 6.31 (s, 1H), 5.13 (ABq , J = 55.5, 16.1 Hz, 2H), 4.81 (ABq, J = 81.0, 9.0 Hz, 2H), 4.24-4.09 (m, 4H) ; 13 C NMR (300 MHz, CDC13) δ 177.5, 155.2, 151.2, 144.6, 144.2, 143.9, 143.8, 141.7, 138.3, 132.2, 128.8, 124.0, 123.7, 120.8, 111.7, 109.1, 99.4, 80.0, 64.5, 63.8, 58.0, 43.7; MS(ES+)m/z387.8(M+ l); for C22H17N3 Analysis calculated for 04: C, 68.21; H, 4.42; N, 10.85. Found: C, 67.81; H, 4.39; N, 10.84. Example 5.17 (8S)-l'-[(2-methoxypyrimidine) -5-yl)methyl]·2,3_dihydrospiro[啥 并[2 3_g][14] benzodioxanthene-8,3·-吲哚]-2,(1Ή)- Ketone synthesis

Following the procedure as described in Example 5.9, and performing an insignificant change, replacing 5-(chlorophenyl) 2-(trifluoromethyl) with 5-(azepine)-2-oxooxypyrimidine hydrochloride ) bite 'and use (8S)_2,3_ dihydrospiro [cough and [2 3 g] [1,4] stupid and dioxererene-8,3·- 哚 哚]-2, ( 1Ή)-ketone replacement 2,3_di-argon snail [e-and-[2,3-g][l,4]benzodioxanthene-8,3'-θ丨哚]-2, (1 ,Η)-_, obtain (8S)-l,-[(2- 143924-sp-20091127-3 •552- 201020257 methoxypyrimidin-5-yl)indolyl]-2,3-dihydrospiro[ Bite and [2,3-g][l,4]benzodioxanthene-8,3W1 p-p]-2·(1Ή)-one (54%), as a colorless solid: melting point 102- 104 °C ; 1H NMR (300 MHz, CDC13) δ 8.56 (s, 2H), 7.30-7.22 (m, 1H), 7.21- 7.15 (m, 1H), 7.11-7.02 (m, 1H), 6.85-6.81 (m, 1H), 6.51 (s, 1H), 6.17 (s, 1H), 4.98-4.77 (m, 3H), 4.66-4.61 (m, 1H), 4.24-4.09 (m, 4H), 4.00 (s , 3H); 13C NMR (300 MHz, CDC13) &lt;5 177.5, 165.4, 158.8, 155.2, 144.7, 141.2, 138.4, 132.2, 128.9, 124.3, 123.9, 122.7, 120.5, 111.4, 108.5, 99.5, 80.1, 64.5 , 63.9, 57.9, 55.1, 38.9: MS (ES+) m/z 417.8 (M+l); calcd for C23 % 9N 305: C, 66, 18; H, 4.59; N, 10.07. Found: C, 65.94; H, 4.68; N, 9.77. 5.18 (8S)-r-(pyrimidin-2-ylindenyl)-2,3-dihydrospiro[1,3-g][l,4]benzodioxanthene-8, Synthesis of 3'-吲哚]ketone

Inconsistent changes were made according to the procedure as described in Example 5.9, replacing 3-(chloromercapto)_2_(trifluoromethyl)pyridine with 2-(azepine)pyrimidine hydrochloride and using (8S) )-2,3-dihydrospiro[,2,3-g][l,4]benzodioxanthene-8,3'-,5丨嗓]-2|(1Ή) - Ketone replacement of 2,3-dihydrospiro [snolo[2,3-g][l,4]benzodioxanthene-8X哚]-2'(1Ή)-one, (8S) -1·-(pyrimidin-2-ylmethyl)-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxene _8,3l吲哚]-πΐΉ)-ketone (59%) ' is a colorless solid: melting point 21〇-212. (: ; iHNMRCSOOMH^CDay δ 8.72-8.68 (m, 2H), 7.23-7.14 (m, 3H), 7.06-6.99 (m, 1H), 6.74-6.69 (m, 143924-sp-20091127-3 -553- 201020257 1H), 6.56 (s, 1H), 6.50 (s, 1H), 5.21 (ABq, J = 82.1, 17.0 Hz, 2H), 4.86 (ABq, J = 81.2, 8.9 Hz, 2H), 4.22-4.10 ( m, 4H) ; 13 C NMR (300 MHz, CDC13) δ 177.8, 164.6, 157.5, 155.1, 144.5, 142.2, 138.2, 132.6, 128.6, 123.8, 1233, 121.5, 119.8, 112.3, 108.7, 99.1, 80.0, 64.5 MS, </ RTI> <RTI ID=0.0></RTI> </ RTI> <RTI ID=0.0></RTI> </RTI> <RTIgt; N, 10.76. Example 5.19 6-Mercapto-1'-(pyridin-2-ylindenyl)-2,3-dihydrospiro[1,4-dioxoindrene[2,3-f]吲哚-8,3,-蚓哚]-2,,7(1Ή,6Η)-dione synthesis®

At 6 °C, 6-methyl-2,3-dihydrospiro[1,4-dioxolynene[2,3-f]indole-8,3'-啕哚]-2 ',7(1Ή,6Η)-dione (0.07 g, 0.21 mmol) in a stirred solution of N,N-dimethylformamide (5 ml), add 12 g of carbonic acid, 〇 61 millimoles). The reaction mixture was stirred at 0&lt;0&gt;C for 30 min, then added &lt;RTI ID=0.0&gt;&gt;&&&&&&&&&&&&&&&&&& . The mixture was diluted with water and ethyl acetate. The organic phase was washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate / hexane (3 / 2) to give 6-methyl-m, _(pyridin-2-yl yl)-2, 3- Hydrogen snail [M-dioxo-area[2,3-f]吲哚_8,3,_吲哚]_2ι,7(1Ή 6η) ^_ (0.02 g, 26%): melting point 87-89 . (:(ethyl acetate/hexane); ih NMR (3〇〇ΜΗζ, 143924-sp-20091127-3 -554· 201020257 CDC13) 5 8.64-8.63 (m, 1H), 7.71-7.62 (m, 2H) , 7.26-7.17 (m, 2H), 6.96- 6.47 (m, 3H), 6.47 (s, 1H), 6.46 (s, 1H), 5.33 (s, 2H), 4.24-4.06 (m, 4H), 3.22 (s, 3H); MS (ES+) m/z 414.0 (M + 1). Example 5.20 yl-1'-{[3-(trifluoromethyl)p-biti-2-yl]methyl}-2 Synthesis of 3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-thirsty]-2Χ1Ή)-one

4'-Fluoro-2,3-dihydrospiro[吱,[2,3$][1,4]benzodioxene-8,3,-吲哚]-2' (1Ή )_嗣(0.31 g, 1.00 mmol), 2_(gas methyl) each (trifluoromethane-based biting hydrochloride (0.29 g, 1.50 mmol) and cesium carbonate (0.98 g, 3.00 mmol) a mixture of Ν, Ν'-dimethylformamide (1 ml), heated at 6 °c for 2 hours and filtered while hot. Cooling the filtrate to ambient temperature and adding water Sediment deposition. The solid was collected by filtration, washed with water (5 mL) ® and dried under vacuum to recrystallize the residue from N,N,-dimethylamine/water. -fluoro-1,-{[3-(trifluoromethyl)p-pyridyl-2-yl]indolyl 2,3_dihydrospich-[2,3-g][l,4 Benzodioxanthene _8,3,_啕哚]-2'(1Ή)-one (0.39 g '82%), as a beige solid: melting point 245_247. 匚; 1H NMR (3 〇〇 MHz , DMSO-de) δ 8.68 (d, J = 4.5 Hz, 1H), 8.27 (d, J = 7.65 Hz, 1H), 7.59 (dd, J = 7.8, 4.9 Hz, 1H), 7.30 (ddd, J = 8.2, 8.2, 5.8 Hz, 1H), 6.86 (d, J = 9.0 Hz, 1H), 6.82 (d, J = 7.8 Hz, 1H), 6.54 (s, 1H), 6.49 (s, 1H), 5.25 (ABq, J = 17.4 Hz, 2H), 4.79 (q, J = 9.4 Hz, 2H), 4.22-4.10 (m, 4H) ; 13 C NMR (75 143924-sp-20091127-3 - 555 - 201020257 MHz, DMSO-d6) δ 176.5, 157.9 (d, 1 JC-F= 247 Hz), 154.6, 152.3, 152.1 (d, 5JC-f= 1-2 Hz), 144.9 (d, 4JC-F= 8.9 Hz), 144.3, 137.6, 135.1 (q, 4 JC.F= 4.9 Hz), 130.8 (d, 4 Jc-F = 8.6 Hz), 125.6 (q, lJc .F= 274 Hz), 123.0, 122.9 (d, 2Jc.f= 32.3 Hz), 119.4, 117.1 (d,3 JC.F= 19.3 Hz), 111.5,109.9 (d, 3 JC.F= 19.9 Hz) , 105.7 (d, 5 JC-F = 2.9 Hz), 98.4, 77.4, 64.1, 63.5, 56.0 (d, 5 Jc. F = 1.7 Hz), 42.3 (q, 5 Jc _ F = 3.3 Hz); MS ( ES+) m/z 460.9 (M + 1). Example 5.21 14(2,2-Difluorocyclopropyl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 ,3'-啕哚]-2·(1Ή)-ketone synthesis

F 2,3-dioxan [吱,[2,3-g][l,4]benzodioxanthene-8,3,-峋哚]-2'(1Ή)-one ( 0.29 g '1.00 mmol), 2-(methylidene)-1,1-difluorocyclopropane (0.21 g ' 1.20 mmol), carbonic acid planer (0.65 g, 2.00 mmol) and hydrazine, A mixture of hydrazine,-dimercaptocaramine (2.5 ml) was heated at 40 °C for 2 hours, and the filtrate was allowed to cool to ambient temperature during the hot transition and water was added to cause deposition of the sink. The solid was collected by filtration, washed with water and dried under vacuum. The residue was recrystallized from ethanol/diethyl ether to give 1,-[(2,2-difluorocyclopropyl)methyl]- 2,3-dihydrospiro-K-[2,3-g][l , 4] benzodioxanthene _8,3,-吲哚]-2,(1Ή)-one (0.28 g, 73%), as colorless solid: mp 162-1641; WNMR (300 MHz, DMSO -d6) 5 7.35 (ddd, J = 7.8, 7.8, 0.9 Hz, 1H), 7.23 (dd, J = 7.9 Hz, 1H), 7.17 (d, J = 6.9 Hz, 1H), 7.06 (dd, J = 7.4, 7.4 Hz, 1H), 6.51 (d, J = 1.9 143924-sp-20091127-3 -556- 201020257

Hz, 1H), 6.13 (d, J = 6.2 Hz, 1H), 4.71 (dd, J = 9.3 Hz, 1H), 4.69 (dd, J = 9.3 Hz, 1H), 4.17 (dd, J = 3.7 Hz, 2H), 4.10 (dd, J = 3.4 Hz, 2H), 3.87 (d, J = 6.9 Hz, 2H), 2.33-2.14 (m, 1H), 1.74-1.60 (m, 1H), 1.48-1.29 (m , 1H); 13 C NMR (75 MHz, DMSO-d6) &lt;5 176.5 (d, 4JC-f = 15.9 Hz), 154.5 (d, 6JC-F = 1.4 Hz), 144.1 (d, 6JC-f= 1.9 Hz), 141.9, 137.7 (d, 5 JC-F= 3.9 Hz), 131.7 (d, 6JC-F=2.3 Hz), 128.8, 123.5, 122.9 (d, 6JC.F=1.6 Hz), 121.2 (d , 5JC.F = 4.1 Hz), 114.3 (q,1 JC-F= 283.4 Hz), 110.9 (d, 2JC-F= 18.1 Hz), 109.1, 98.7 (d,5 JC_F= 3.6 Hz), 79.2 (d , 5 Jc-F= 3.7 Hz), 64, 1, 63.5, 57.1 (d, 6JC-F = 2.4 β Hz), 36.6 (t, 3 Jc-F = 5.9 Hz), 20.1 (t, 2JC-F= 17.4 Hz), 14.7 (t, 2 Jc-F = 10.7 Hz); MS (ES+) m/z 386.2 (M + 1). Example 5.22 1'-Mercapto-2,3-dihydrospiro[啥,[2,3-g][l,4]benzodioxene-8,3'-吲哚]-2' (1Ή)-ketone synthesis

Displacement of 2-(bromodecyl)-1,1-difluorocyclopropane using dimethyl sulfate in accordance with the procedure described in Example 5.21 and subject to insignificant changes to obtain 1'-methyl-2. 3-Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8, 啕哚]-2·(1Ή)-one (28%), as a colorless solid: 152-154°C; iHNMROOO MHz, DMSO-d6) δ 734 (d, J = 7.6 Hz, 1H), 7.15-7.01 (m, 3H), 6.50 (s, 1H), 6.18 (s, 1H), 4.67 (d, J = 9.3 Hz, 2H), 4.13 (dd, J = 4.5, 2.8 Hz, 4H), 3.14 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.9, 155.1, 144.5, 143.7, 138.2, 132.2, 129.2, 123.7, 123.3, 121.7, 111.8, 109.3, 99.1, 79.9, 64.6, 64.0, 143924-sp-20091127-3 -557- 201020257 57.6, 26.9 ; MS (ES+) m/z 310.2 ( Μ + 1). Example 5.23 Γ-{[4-(Trifluoromethyl) 4,3_oxazol-2-yl] fluorenyl}_2,3_dihydrospiro[吱,[2,3-g][l,4 Synthesis of benzodioxanthene _8,3,_ 朵朵]_2,(1Ή)__

Following the procedure as described in Example 5.21, and applying an insignificant change, 2-(bromomethyl)-4-(trifluoromethyl)pyrazole was substituted for 2_(bromomethyl) sense: ^2 Fluorocyclopropane, obtained Γ-{[4-(trifluoromethyl)_ι, 3_ρ-----[pyridin-2-yl]]yl}-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene _8,3,_吲哚]-2,(1Ή)-net (58%), colorless solid: melting point 169-17 (TC; 4 NMR (300 MHz, DMSO-d6) δ 8.49 (s, 1Η), 7.32 (dd, J = 7.7, 7.7 Hz, 1H), 7.21 (d, J = 6.9 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 7.08 (dd, J = 7.3, 7.3 Hz, 1H), 6.53 (s, 1H), 6.22 (s, 1H), 5.36 (ABq, J = 16.9 Hz, 2H), 4.74 (dd, J = 9.4 Hz, 2H ), 4.14 (dd, J = 4.7, 3.1 Hz, 4H); 13C NMR (75 MHz, DMSO-de) &lt;5 176.5, 168.6, 154.5, 144.1, 143.3, 142.2 (d, 2 JC-F = 36.5 Hz ), 137.8, 131.6, 128.8, 124.5 (q, 3 JC-F= 6.6 Hz), 123.7, 123.4, 120.9, 120.3 (q, 1JC-f= 270 Hz), 111.1, 109.1, 98.7, 79.2, 64.1, 63.5 , 57.1, 41.1; MS (ES+) m/z 460.9 (M + 1). Example 5.24 (2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4 Benzodioxanthine -8,3Ή1 indol] -Γ (2Ή) - yl) acetonitrile The synthesis 143924-sp-20091127-3 -558 · 201020257

Following the procedure as described in Example 5.9, and carrying out an insignificant change, 2-(a)methyl- 6-(trifluoromethyl)pyridine was replaced with bromoacetonitrile to give (2·-keto-2, 3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-β哚]-1'(2Ή)-yl)acetonitrile (54% , as a colorless solid: mp 161-162 ° C (diethyl ether); 4 NMR (300 MHz, CDC13) δ 7.35-7.38 (m, 1H), 7.23-7.10 (m, 2H), 7.04 (d, J ❹ = 7.8 Hz, 1H), 6.48 (s, 1H), 6.21 (s, 1H), 4.87 (d, J = 9.1 Hz, 1H), 4.67 (d, J = 3.7 Hz, 2H), 4.63 (d, J = 9.1 Hz, 1H), 4.20-4.05 (m, 4H); 13C NMR (75 MHz, CDC13) δ 176.6, 155.2, 144.9, 139.7, 138.5, 131.6, 129.3, 124.8, 124.4, 120.1, 113.6, 111.6, 108.7, 99.6, 79.9, 64.5, 63.9, 57.9, 28.0; MS (ES+) m/z 334.9 (M + 1). Example 5.25 9-Fluoro-fluorenyl-(10)pyridin-2-ylindenyl)-2,3-dihydro-spiro[N,3-g][l,4]benzodioxanthene Synthesis of -8,3'-吲哚]-2,(1Ή)-ketone

In a 503⁄4 liter round bottom flask filled with 9-fluoro 2,3-dihydrospib- oxa[2,3-g][l,4]benzodioxanthene _8,3,,哚]_2, (1Ή) class (〇63 g, 2 〇 mmol), 2-(bromo fluorenyl azidine hydrobromide (〇 51 g, 2 〇 millimolar), dimercaptocarbonate Indoleamine (20 ml). The mixture was allowed to cool to ambient temperature, passed (3.26 g, 10.0 mmol) and ν, Ν-bis mixture was heated at 90 C for 1 hour, 143924-sp.20091127 -3 -559· 201020257 Filtration and concentration of the filtrate in vacuo. The residue was purified by column chromatography eluting with EtOAc EtOAc EtOAc EtOAc Fluoro-indole-0-pyridin-2-ylindenyl)-2,3-dihydro-spiro[吱,[2,3-g][i,4]benzodioxanthene-8, 3W 丨哚]-2·(1Ή)-ketone (0.46 g, 57%), mp.: NMR (300 MHz, DMSO-dg) δ 8.45 (d, J = 4.3 Hz, 1H), 7.71-7.77 (m, 1H), 7.40-6.87 (m, 6H), 6.19 (d, J = 1.8 Hz, 1H), 5.02 (ABq, 2H), 4.84 (ABq, 2H), 4.27-4.09 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 176.7, 155.6, 149.6, 143.1, 142.1, 142 .0, 139.2, 139.2, 138.5, 137.5, 135.3, 133.9, 133.7, 131.5, 129.3, 124.1, 123.4, 123.2, 122.7, 122.7, 122.1, 109.9, 106.6, 106.6, 80.8, 64.7, 64.1, 58.0, 58.0, 45.2 ; MS (ES+) m/z 404.8 (M + 1). Example 5.26 9-lactyl-1 -{[3-(di-mercapto)p-buty-2-yl]fluorenyl}-2,3-diaza snail [bito-and-[2,3-g][ Synthesis of l,4]benzoxantheneene-8J-吲哚]-2'(1Ή)-one

Displacement of 2-(bromomethyl)pyridinium hydrochloride with 2-(chloromercapto)-3-(trifluoromethyl)pyridine hydrochloride according to the procedure as described in Example 5.25 and subject to insignificant changes Bromate, 9-fluoro-indenyl-{[3-(trifluoromethyl)pyridin-2-yl]indolyl}-2,3-dihydrospiro[吱,[2,3-g] [l,4]benzodioxanthene-8,3'-indole]-2'(1Ή)-one (25%) as colorless solid: iHNMRGOOMHtDMSO^) (5 8.62 (d, J = 4.3) Hz, 1H), 8.21 (d, J = 7.4 Hz, 1H), 7.53 (dd, J = 7.7, 5.0 Hz, 1H), 7.28-6.83 (m, 4H), 6.29 (d, J = 1.8 Hz, 1H ), 5.20 (ABq, 2H), 4.84 (ABq, 2H), 4.27-4.10 143924-sp-20091127-3 -560· 201020257

(m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.9, 152.8, 143.4, 142.0, 141.9, 139.2, 139.2, 138.5, 135.5, 135.4, 135.4, 135.2, 133.9, 133.7, 131.5, 129.3, 126.1 , 124.1, 123.7, 123.4, 123.4, 123.2, 122.8, 122.8, 122.5, 109.6, 106.8, 106.8, 80.6, 64.7, 64.1, 58.0, 58.0, 42.4, 42.4; MS (ES+) m/z 472.9 (M example 5.27 9 -fluoro-l'-[(5-hydroxypyridin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxan Synthesis of terpenes-8,3W丨哚]-2·(1Ή)-ketone

Following the procedure as described in Example 5.25, and applying an insignificant change, 5-(;oxy)-2-(chloromethylcyclopyridine hydrochloride was substituted for 2_(bromomethyl oxaridinium hydrobromic acid) Salt, obtain 1'-{[5-(- yloxy azolidine-2-yl)methyl}_9_fluoro-2,3_dihydrospiro [bite-and-[2,3-g][l,4 Benzodioxanthene _8,3,_吲哚]_2,(1Ή)__ (59%) ' is a colorless solid: MS (ES+) m/z 511,0 (Μ + 1). The last step is -([5_(oxy acridine-2-yl)methylbu 9-carbyl-2,3-dihydrospiro[吱'[2'3-g][l,4] Benzodioxanthene _8,3'_吲哚]_2, (1Ή)-ketone palladium/carbon (1〇% w/w, 0.2g), decyl alcohol (50ml) and acetic acid (1 drop) The mixture was hydrogenated at ambient temperature for 5 hours under ambient pressure. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate In the 0% to 70% gradient solution, 9-fluoro-1 -[(5-hydroxypyridin-2-yl)indolyl]-2,3-dihydrospiro[; 3 g][1,4]benzo 143924-sp-20091127-3 •561 - 201020257 Dioxetene-8,3'-吲哚]-2 '(1 Ή)-ketone (0.37 g, 46%) as an off-white solid: :H NMR (300 MHz, DMSO-d6) &lt;5 9.88 (s, 1H), 8.00 (d, J = 2.6 Hz, 1H ), 7.25-7.09 (m, 4H), 7.01-6.87 (m, 2H), 6.12 (d, J = 1.8 Hz, 1H), 4.88 (ABq, 2H), 4.82 (ABq, 2H), 4.29-4.09 ( m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.0, 152.8, 145.2, 142.6, 141.5, 141.4, 138.7, 138.0, 137.1, 134.8, 133.4, 133.2, 131.0, 128.8, 123.5, 123.0, 122.8, 122.4, 122.2, 109.5, 106.0, 80.2, * 64.3, 63.6, 57.5, 44.2; MS (ES+) m/z 421.1 (M + 1). Example 5.28 Γ-(ρ ratio bit-2-yl fluorenyl)-7 ,8-Dihydro-6H-spiro-[p-mono-[2,3-g] octazone-3,3'-p5| 哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 5.25, and with irrelevant changes, use 7,8-dihydro-6Η-spiro [snolo[2,3-g]nonene-3,3'-4哚] -2Χ1Η)-keto-substituted 9-fluoro-2,3-dihydro-spiro[吱,[2,3-g][l,4]benzodioxolene-8,341 哚]-2' ( 1Ή)-ketone' obtained Γ-(acridin-2-ylmethyl)-7,8-dihydro-6H-spiro-[furo[2,3-g]nonene-3,3'-啕哚]-2·(1Ή)-嗣(87%), as an off-white solid: 1H NMR (300 MHz, DMSO-d6) δ 8.46 (d, J = 4.8 Hz, 1H), 7.71-7.77 (m, 1H), 7.37-6.88 (m, 6H), 6.64 (s, 1H), 6.18 (s, 1H), 5.03 (ABq, 2H), 4.72 (ABq, 2H), 4.04-3.84 (m, 2H), 2.66 (t, J = 6.4 Hz, 2H), 1.88-1.67 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 177.1, 155.7, 154.3, 149.7, 149.4, 143.0, 137.5, 132.3, 129.1, 128.6, 123.9, 123.6, 123.4, 123.1, 122.0, 111.5, 110.4, 143924-sp-20091127-3 • 562- 201020257 109,8,79,3,66.2,58.0,45.2,25.2,22.1; MS(ES+)m/z384.8 (M+l). Example 5.29 1 -{[3-(dimethyl fluorenyl)p butyl-2-yl] fluorenyl}-7,8-diaza-6H-spiro [bito-and-[2,3-g] decene- Synthesis of 3,3W丨哚]-2'(1Ή)-®Ι

Refer to the procedure described in Example 5.25 and perform irrelevant changes using 7,8-dihydro-6Η-spiro[吱,[2,3-g] acetylene-3,3,-吲哚]-2,(1Η)-keto-substituted 9-fluoro-2,3-dihydro-spiro[吱,[2,3-g][l,4]benzodioxanthene_8,3W丨p木]-2 (1H)- Brewing I' and using 2-(methylmethyl)-3-(trifluoromethyl)p to bite hydrochloride to displace 2-(bromomethyl)acridine hydrogen Bromate, obtained trifluoromethyl)p-pyridin-2-yl]fluorenyl}-7,8-dihydro-6H-spiro[pyrano[2,3-g]nonene-3,3, -吲哚]-2,(1Ή)-one (2%) as a colorless solid: iHNMR (300MHz, DMSO-d6) (5 8.65 (d, J = 4.4 Hz, 1H), 8.25 (d, J = 7.8 Hz, 1H), 7.56 (dd, J = 7.8, 5.0 Hz, 1H), 7.20-7.26 φ (m, 1H), 7.15 (d, J = 6.9 Hz, 1H), 7.01 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.65 (s, 1H), 6.31 (s, 1H), 5.22 (ABq, J = 39.2 Hz, 2H), 4.72 (ABq, J = 18.8 Hz, 2H), 4.04-3.95 (m, 2H), 2.70 (t, J = 6.4 Hz, 2H), 1.89-1.77 (m, 2H); 13C NMR (75 MHz, DMSO-de) δ 177.1, 155.7, 154.3, 149.7, 149.4, 143.0, 137.5, 132.3, 129.1, 128.6, 123.9, 123.6, 123.4, 123.1, 122.0 , 111.5, 110.4, 109.8, 79.3, 66.2, 58.0, 45.2, 25.2, 22.1; MS (ES+) m/z 453.2 (M+l). Example 5.30 2-[(2'-keto-2,3-di Hydrogen snail [吱,[2,3-phan [1,4] benzodioxanthene-8,3'- 143924-sp-20091127-3 •563· 201020257 啕哚Η·(2Ή)-based Synthesis of fluorenyl] acridine-3-carboxylic acid ethyl ester

In a 50 ml round bottom flask, filled with 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3,-啕哚]-2 , (1Ή)-ketone (2.0 g, 6.8 mmol), 2-(Moalylmethyl) nicotinic acid ethyl ester (2.3 g, 9.4 mmol), cesium carbonate (6.62 g, 20.3 mmol) , Essence clock (0.17 g, 1.0 mmol) and hydrazine, hydrazine-dimethyl decylamine (3 ginseng ml). The reaction mixture was stirred under nitrogen at 95 ° C for 1 hour, cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography and dissolved in a gradient of 醋酸% to 3〇% of ethyl acetate in dioxane to obtain 2-[(2'-keto-2,3-dihydro) Snail [吱,[2,3-g][l,4]benzodioxanthene _8'3'-蚓哚]-Γ(2Ή)-yl)methyl&gt; Ethyl carboxylate (2.4 g, 79%), mp. Example 5.31 1-(Pyridin-2-ylmethyl)spiroindole-3,3% dexeno[2,3-f][l]benzofuran]-2(1H)-indolone 5,5' - Synthesis of dioxide

According to the procedure as described in Example 5.25, and with irrelevant changes, use spiro 51哚-3,3'-sulfeno[2,3-f][i] benzofuran]·2(ΐΗ) -« 5,5,-dioxide 143924-sp-20091127-3 -564- 201020257 Substituting 9-fluoro-2,3-dihydro-spiro[furo[2,3_g][1,4]benzo Dioxetene-8,3'-♦1](1Ή)-one, which gives 1-7-pyridyl-2-ylindole) snail _3,3, far-directed [2'3 -f][l]benzofuran]-2(1H)-one 5,5,-dioxide (43%) as an off-white solid: 1H NMR (300MHz, CDC13) 5 8.44 (d, J = 4.8 Hz , 1H), 7.87-6.91 (m, 11H), 5.11 (ABq, 2H), 4.96 (ABq, 2H); 13C NMR (75 MHz, CDC13) δ 176.0, 165.5, 155.2, 149.4, 143.0, 137.6, 134.3, 131.1, 129.9, 129.1, 128.6, 128.5, 126.4, 124.4, 124.1, 123.8, 123.3, 122.9, 111.4, 110.4, 81.3, 56.4, 44.8; MS (ES+) m/z 416.9 (Μ + 1). Example 5.32 Γ-(pyrimidin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3_§][1,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-鲷 Synthesis

Follow the procedure as described in Example 5, and perform irrelevant changes, © using 2, quinone dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8 ,3,_吲哚]-2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[i,2-b:5,4-7,]difuran-3,3,-啕嗓] -2'(1Ή)-_, and replacing 5-(ylmethyl)-2-methoxypyrimidine with 2-(chloromethyl)pyrimidine hydrochloride to obtain Γ_(pyridin-2-ylmethyl) _2,3_dihydrospiro[ρ, s-[2,3-g][l,4]benzodioxolene _8,3,_吲哚] (9〇%): melting point 278- 279〇C ; 1H NMR (300 MHz, CDC13) δ 8.67 (d, J = 4.9 Hz, 2H), 7.20-7.11 (m, 3H), 7.05-6.94 (m, 1H), 6.72-6.67 (m, 1H ), 6.54 (s, 1H), 6.47 (s, 1H), 5.19 (ABq, 2H), 4.83 (ABq, 2H), 4.21-4.02 (m, 4H) ; 13 C NMR (75 143924-sp-20091127- 3 • 565- 201020257 MHz, CDC13) δ 177.8, 164.6, 157.5, 155.1, 144.5, 142.2, 138.2, 132.6, 128.6, 123.8, 123.3, 121.5, 119.8, 112.3, 108.7, 99.1, 80.0, 64.5, 63.9, 58.1, 45.7 ; MS (ES+) m/z 387.9 (M + 1). Example 5.33 Γ-[(4,6-Dioxalylpyrimidin-2-yl)methyl]-2,3-dihydrospiro[pfrano[2,3-g][l,4] benzo Synthesis of Dioxetine-8,3·-啕哚]-ΑΓΗ)-one

According to the procedure as described in Example 5, and irrelevant changes were made, 2'3-dihydrospiro[2,3-g][l,4]benzodioxanthene was used. ]_ 2'(1Ή)-keto-substituted 5,6-dihydrospiro[benzo[l,2-b:5,4-7,]difuran-3,3'-蚓哚]- 2'(1Ή) -ketone' and the use of 2-(chloromercapto)-4,6-dimethoxypyrimidine to replace 5-(azepine)-2-methoxypyrimidine' to obtain Γ-[(4,6_2曱oxypyrimidin-2-yl)methyl]_ 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene_8,3,-吲哚]-2,(1Ή)-ketone (90%): melting point 169-170 ° C; iHNMRGOOMHtCDClg) (5 7.21-7.11 (m, 2H), 7.06-6.95 (m, 1H), 6.81-6.67 (m, 1H), 6.49 (s, 1H), 6.37 (s, 1H), 5.89 (s, 1H), 4.98 (ABq, 2H), 4.80 (ABq, 2H), 4.23-4.00 (m, 4H), 3.80 (s , 6H) ; MS (ES+) m/z 447.9 (M + 1). Example 5.34 6-(2-methoxyethoxy)-indole-indolepyridin-2-ylmethyl) spiro[l-benzene Synthesis of furan_3,3,_ρ丨哚丨哚]-2'(1Ή)-ketone 143924-sp-20091127-3 -566- 201020257

According to the procedure as described in Example 5, and irrelevant changes were made, using 6-(2-methoxyethoxy)spiro[i_benzofuran], ketone substitution 5,6- Dihydrospiro[benzo[i,2-b:5,4h']difuran-3,3Wbido]-2,(1Ή)-one, and 2-(bromomethyl)pyridine hydrobromide Replacement of 5_(chloromethyl)_2-methoxypyrimidine with acid salt to obtain 6-(2-decyloxyethoxy)_r_(P-pyridyl-2-ylmethyl) snail benzofuran® 3,3,-♦来来-2,(1Ή)-ketone (72%): melting point 94-95 ° C; NMR (300 ΜΗζ, CDC13) δ 8.56 (d, J = 4.7 Hz, 1H), Ί. 69-7.59 (m, 1H), 7.25-7.09 (m, 4H), 7.05-6.95 (m, 1H), 6.92-6.82 (m, 2H), 6.81-6.73 (m, 1H), 6.37 (s, 1H ), 5.08 (ABq, 2H), 4.83 (ABq, 2H), 3.93 (t, J = 4.7 Hz, 2H), 3.62 (t, J = 4.7 Hz, 2H), 3.36 (s, 3H) ; 13C NMR ( 75 MHz, CDC13) δ 1112, 155.5, 155.1, 153.7, 149.5, 142.1, 137.1, 132.0, 129.6, 128.9, 123.8, 123.5, 122.8, 121.6, 115.8, 110.5, 110.4, 109.5, 79.8, 71.0, 68.1, 59.1, 58.5, 46.1 ; MS (ES+) m/z 403.0 (M + l). Example 5.35 Synthesis of 5-(2-methoxyethoxypyridin-2-ylmethyl)spiro tl_benzofuran_3,3l吲 哚]-2'(1Ή)-one

Follow the procedure as described in Example 5, and perform an insignificant change 'Using 5-(2-methoxyethoxy)spirobenzofuran_3,3,_吲哚]-2, (1Ή) - 嗣 143924^sp-20091127-3 567· 201020257 For 5,6-dihydrospiro [benzo[i,2-b : 5,4-b,]difuran-3,3,-吲哚]- 2'(1Ή)-one, and 5-(bromomethyl)-2-methoxypyrimidine is replaced with 2-(bromomethyl)pyridine hydrobromide to obtain 5-(2-methoxyethoxy) )-Γ-(pyridin-2-ylindenyl)spiro[1-benzofuran-3,3'-indole]-2'(1Ή)-one (65%): m.p. 140-142. (: ; 1H NMR (300 MHz, CDC13) δ 8.57 (d, J = 4.8 Hz, 1H), 7.65 (t, J = 7.6 Hz, 1H), 7.25-7.11 (m, 4H), 7.06-6.97 (m , 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.68-6.62 (m, 1H), 6.59-6.54 (m, 1H), 6.44-6.38 (m, 1H), 5.09 (ABq, 2H), 4.87 (ABq, 2H), 4.11-4.05 (m, 2H), 3.77-3.68 (m, 2H), 3.43 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 177.6, 162.1, 160.7, 155.6, 149.5 , 142.1, 137.0, 132.4, 128.8, 123.8, 123.6, 123.5, 122.7, 121.6, 121.1, 109.5, 108.2, 97.3, 80.5, 70.9, 67.6, 59.2, 57.7, 46.1; MS (ES+) m/z 403.0 (M + 1) Example 5.36 Γ-0-pyridin-2-ylindenyl)-2,3-dihydrospiro[N,3-f][i,4]benzodioxene-7J -吲哚]-2'(1'H)-ketone synthesis

2,3-Dihydrospiro[吱,[2,3-f][l,4]benzodioxanthene was used according to the procedure described in Example 5.30, and irrelevant changes were applied. _7,3,-4丨哚]-2'(1Ή)-ketones are substituted for 2,3-dihydrospiro[, succinyl[2,3_g][1,4]|dioxordecene-8, 3'-θ丨嗓]-2'(1Ή)-ketone' and 2-(bromomethyl)-substituted ethyl 2-(bromomethyl) Pyridin-2-ylmethyl)_2,3_dihydrospiro[吱,[2,3-f][l,4]benzodioxene _7,3,(5)哚]_2, (1Ή Ketone (57%), 143924-sp-20091127-3 -568· 201020257 is a colorless solid: melting point 205-206 ° C; 1H NMR (300 MHz, DMSO-d6) (5 8.52 (d, 1H, J = 4.7 Hz) , 7.79 (ddd, J = 7.7, 7.7, 1.7 Hz, 1H), 7.35-7.20 (m, 4H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 6.93 (d, J = 7.7 Hz, 1H ), 6.29 (ABq, 2H), 5.04 (ABq, 2H), 4.84 (ABq, 2H), 4.27 (s, 4H) ; 1 3 C NMR (75 MHz, DMSO-d6) δ 176.7, 155.2, 149.2, 148.8 , 144.6, 142.5, 137.0, 131.6, 129.2, 128.6, 123.6, 122.9, 122.6, 122.4, 121.4, 114.4, 109.8, 109.2, 80.2, 64.1, 63.9, 57.3, 44.8; MS (ES+) m/z 387.7 (M + 1) 〇 Example 5.37 ❹ 1L{[3-(Trifluoromethylcyclopyridin-2-yl)methyl}-2,3-dihydrospiro[吱,[2,3-f][l,4] benzodiazepine Synthesis of Oxygen-ene-7,3'-吲哚]-2Χ1Ή)-one

(3-(Trifluoromethylidin-2-yl)nonanol hydrochloride (0.324 g, 1.52 mmol φ) and disulfide sulfoxide (0.174 mL, 2.39 mmol) in anhydrous A mixture of chlorodecane (10 ml) was stirred at ambient temperature for 16 h. The reaction mixture was concentrated in vacuo</RTI> and EtOAc &lt;RTI ID=0.0&gt; , adding 2,3-dihydrospiro[ρ, s-[2,3-f][i,4]benzodioxanthene-7,3'-吲哚]-2'(1Ή)-_ (0.300 g,;!. 01 mmol), carbonic acid (0.926 g, 2.84 mmol), moth (0.094 g, 0.57 mmol) and anhydrous N,N-dimethylformamide ( 15 ml), and the mixture was heated at 9 Torr for 1 hour. The reaction mixture was cooled to ambient temperature, concentrated in vacuo, and the residue was dissolved in water (50 mL). Filtration. 143924-SP-20091127-3 • 569- 201020257 solids were purified by column chromatography and eluted with ethyl acetate in a 0% to 40% gradient in di-methane, followed by recrystallization from methanol. Trifluoromethyl)pyridine-2- ]methyl}-2,3-dihydrospiro[吱,[2,3-f][l,4]benzodioxene-7,3·-吲哚]-2·(1Ή) - 嗣 (0.123 g, 27%), as colorless solid: m.p.: s.sup.ssssssssssssssssssssssssssssssssssssssssssssss 7.9 Hz, 1H), 7.55 (dd, J = 7.8, 5.0 Hz, 1H), 7.26-7.20 (m, 2H), 7.01 (dd, J = 11.3, 3.8 Hz, 1H), 6.88 (d, J = 7.6 Hz, 1H), 6.36 (s, 2H), 5.22 (ABq, 2H), 4.83 (ABq, 2H), 4.27 (s, 4H) ; 13C NMR (75 MHz, DMSO-d6) 5 177.0, 152.6, 152.4, 148.7, 144.6, 142.9, 134.9, 131.7, 129.1, 128.6, 123.5, 123.0, 122.8,

122.6, 122.5, 122.0, 114.8, 110.0, 108.9, 80.1, 64.1, 63.9, 57.3, 41.8; MS (ES+) m/z 455.0 (M + 1). Example 5.38 6-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxolene]_7,3'_4 哚]_ι,(2,Η)- Synthesis of methyl]pyrimidine-2,4(1H,3H>dione

Displacement of 2-(bromohydrazino)p-pyridinium hydrobromide with 6-(carbylmercapto)uracil according to the procedure described in Example 5.25 and with irrelevant changes, and use of snails [吱Ando[2,3-f][l,3]benzodioxanthene_7,3,-峋哚]-2,(1Ή)-one is substituted for 9-fluoro-2,3-dihydrogen - spiro [furo[2,3_g][1,4]benzodioxanthene-8,34哚]-2'(ΓΗ)-one, 6-[(2'-oxo[[2] And [2,3-f][l,3]benzodioxanthene-7,3'-(f)哚]-1'(2Ή)-yl)methyl]ergidine-2,4(1H, 3H)-dione (5%), 143924-sp-20091127-3 -570-201020257 off-white solid: melting point &gt; 300 ° C; iHNMRGOOMHtDMSO-dg) 5 11.11 (s, 1H), 11.05 (s, 1H) , 7.29 (dd, J = 7.7, 7.7 Hz, 1H), 7.18 (d, J = 6.8 Hz, 1H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 7.03 (dd, J = 7.7, 7.7 Hz, 1H), 6.66 (s, 1H), 6.26 (s, 1H), 5.90 (s, 2H), 5.14 (s, 1H), 4.75 (ABq, 2H), 4.60 (ABq, 2H); 13C NMR ( 75 MHz, DMSO-d6) δ 177.4, 164.2, 155.9, 151.8, 151.5, 148.8, 142.3, 142.2, 132.1, 129.4, 124.2, 123.9, 120.1, 109.8, 103.6, 101.9, 96.9, 93.8, 80.4, 57.9, 40.5; MS (ES+ ) m/z 406.3 (M + 1). Example 6 ® 14 (5-alkyl-l,2,4-p-soxadiazol-3-yl)indolyl] spirono[2,3-f][l,3]benzodioxanthene Synthesis of alkene-7,3·-啕哚]-2·(1Ή)-one

In the snail [biting and [2,3-f][l,3] stupid and dioxynene-7,3,-吲哚]-2'(1Ή)-one (1.33 g ' 4.73 mmol) ) in acetone (50 ml) and 2-butanone (1 ml) in a stirred solution of 'addition of carbonic acid planing (3.10 g, 9.46 mmol) with 5-carbon-3-(chloromethyl) )-1,2,4- far diazole (1,00 g, 5.92 mmol). The reaction was stirred at ambient temperature for 16 h then filtered and concentrated in vacuo to dryness. The residue was purified by flash chromatography using ethyl acetate (15% to 50% gradient) in hexanes to give a gas base::^^^^^^^^^^^^^^^^^ Ρ-vectors[2,3-f][l,3]benzodioxol-7,3,-吲哚]-2,(1Ή)-one (0.43 g '22%), colorless Solid: melting point 4 NMR (300 MHz, DMSO-d6) δ 7.29 (dd, J = 7.7, 7.7 Hz, 1H), 7.21 (d, J = 7.0 Hz, 1H), 7.08-7.03 (m, 2H), 6.71 (s, 1H), 6.32 (s, 1H), 5.93 (d, J = 3.0 Hz, 2H), 5.24 143924-sp-2CX) 91127-3 •571- 201020257 (ABq, 2H), 4.78 (ABq, 2H 13C NMR (75 MHz, DMSO-d6) δ Ml2, 174.2, 170.6, 155.7, 148.8, 142.4, 142.2, 132.2, 129.3, 124.1, 123.7, 120.4, 109.8, 103.5, 101.9, 93.8, 79.9, 57.9, 41.6 MS (ES+) m/z 414.1 (M + 1), 416.1 (M + 1). Example 6.1 4'-Chloro-indole-[(5-chloro-1,2,4-diazol-3-yl)methyl] snail [吱叫[2,3-f][l,3 Synthesis of benzodioxanthene-7,3·-(9)哚]-2'(1Ή)-one

Following the procedure as described in Example 6, and applying an insignificant change, 4'-gas-based spiro[吱,[2,3-f][l,3]benzodioxol-7, 3,-W哚]-Ζ(1Ή)-ketone-substituted snail [吱,[2,3-f][l,3]benzodioxene-7,3,·吲哚]-2\ 1 Ή)-ketone, obtaining chloro-indole-[(5-chloro-l,2,4-p-soxadiazol-3-yl)methyl] snail [p-fol-[2,3-f][ l,3]benzodioxene-7,3,-峋哚]-2,(1Ή)-one (17%), as a colorless solid: mp 174-176 ° C; iHNMRGOOMHz 'DCiy 5 7.17 ( Dd, J = 8.0 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 6.67 (d, J = 7.8 Hz, 1H), 6.46 (s, 1H), 6.34 (s, 1H), 5.86 ( ABq, 2H), 5.16 (ABq, 2H), 4.95 (ABq, 2H); 13C NMR (75 MHz, CDC13) 5 177.2, 174.9, 169.4, 156.8, 149.2, 143.3, 142.1, 131.7, 130.1, 128.4, 124.5, 166.5, 107.2, 103.2, 101.5, 93.2, 77.2, 58.8, 41.6; MS (ES+) m/z 447.9 (M + 1), 449.9 (M + 1). Example 6.2 5,6-Dimethyl-indole-(tetrahydro-2H-pyran-2-ylmethyl)spiro[1-benzopyran-3,3,-吲143924-sp-20091127-3 - 572- 201020257 嗓]-2'(ΓΗ)-ketone synthesis

Knowing the procedure as described in Example 6, and performing irrelevant changes, using 5,6-monomethylspirobenzofuran-3,3, anthraquinone to replace the snail [biting and squeezing [2'3 -f][l'3]benzodioxanthene _7,3,(4)哚]_2, (1Ή), and 2-(bromoindenyl)-tetrahydro-2-indole-pericyclic substitution 5 _Chloryl_3_(gasylmethyl)^di+thiazolyl, 5,6-diindenyl-ι'_(tetrahydro-2Η_喊喃_2_ylindenyl) snail to benzofuran Chew -3,3'-dead]-2'(1'Η)-ketone (72%) as a colorless solid: iH nmr (3〇〇ΜΗζ, CDC13) δ 7.28 (dd, J = 7.6, 7.6 Hz , 1H), 7.15-6.97 (m, 1H), 6.75 (s, 1H), 6.47 (d, J = 4.9 Hz, 1H), 4.89 (dd, J = 8.9, 1.8 Hz, 1H), 4.65 (dd, J = 8.9, 2.9 Hz, 1H), 4.03-3.60 (m, 2H), 3.44-3.32 (m, 1H), 2.19 (s, 3H), 2.05 (s, 3H), 1.92-1.80 (m, 1H) , 1.73-1.27 (m, 1H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 159.1, 143.2, 138.3, 132.6, 129.3, 128.6, 126.3, 123.9, 123.6, 123.1, 111.4, 109.7, 79.7, 75.6, 68.4 , 58.0, 45.7, 29.6, 25.8, 23.0, 20.3, 19.4; MS (ES+) m/z 364.3 (M + 1). Example 6.3 1·-[(3-Chlorosulfenyl-2-yl)indolyl] snail [吱,[2,3-f][l,3]benzodioxene-7,3' -吲哚]-2'(1Ή)-ketone synthesis

143924-sp-20091127-3 -573- 201020257 According to the procedure as described in Example 6, and with irrelevant changes, 3-chloro-2-ylmethyl p-cetin (Morton et al. Leii. 2000), 41: 3029-3034) Displacement of 5-gasyl-3-(alkylmethyl-soxadiazole to obtain Γ-[(3-carbyl sulfen-2-yl) fluorenyl] snail [2,3-f][l,3]benzodioxanthene-7,3,-啕哚]-2'(1Ή)-steel (38%), as an off-white solid: melting point 161_163 °c; iHNMR (300 MHz, CDC13) δ 7.29-7.20 (m, 2Η), 7.15 (d, J = 7.3 Hz, 1H), 7.08-6.93 (m, 2H), 6.88 (d, J = 5.2 Hz, 1H), 6.51 (s, 1H), 6.16 (s, 1H), 5.86 (d, J = 2.7 Hz, 2H), 5.09 (ABq, 2H), 4.80 (ABq, 2H) ; 13 C NMR (75 MHz, CDC13 ) δ 177.3, 156.0, 148.9, 142.4, 141.2, 132.1, 131.4, 129.0, 127.6, 125.1, 124.1, 124.0, 123.7, 119.3, 109.2, 103.2, 101.5, 93.6, 80.5, 58.3, 37.0 ; MS (ES+) m/z 412.1 (M + 1). Example 6.4 Γ-{[3-(2,6-di-phenylphenyl)-5-methylisoxazole _4_yl] fluorenyl} snail [biting mer to [2,3- f][l,3] stupid and dioxolene _7,3,_P 哚]_2, (1Ή)__ synthesis

Following the procedure as described in Example 6, and carrying out an insignificant change, the 5-chloro group was replaced with 4-(aeromethyl)-3(2,6-diphenyl)-5 methyliso-oxazole. 3-(methylmethyl)-1,2,4-ρ stopper diazole, and using acetone as a solvent to obtain Γ-{[3-(2'6-diphenyl)-5-methylisoxazole _4_基]methyl} snail [biting 〇 〇 [ [1'3] benzodioxolane _7,3,_吲哚]_2, (1Ή)__ (71%), is a colorless solid : melting point 190-192 ° C; iH NMR (300 MHz, CDC13) (5 7.39-7.22 (m, 3 Η), 143924-sp-20091127-3 • 574- 201020257 7.10-7.01 (m, 1H), 7.00-6.88 (m, 2H), 6.46 (s, 1H), 6.20 (d, J = 8.2 Hz, 1H), 6.02 (s, 1H), 5.83 (d, J = 4.1 Hz, 2H), 4.59 (ABq, 2H) , δ 177.4, 169.2, 158.6, 156.0, 148.9 128.1, 127.9, 123.9, 123.2, 119.0, 110.2, 107.7, 103.1, 101.5, 93.6, 80.6, 57.9, 33.3, 11.7; MS (ES+) m/z 521.3 (M + 1), 523.3 (M + 1). 6.5 1'-({2-[4-(Trifluoromethyl)phenyl]-i, 3_P 塞 _4_ yl} fluorenyl) Synthesis of snail [吱味和 ® [2,3-f][l,3]benzodioxanthene-7,3·-啕哚]-2·(1Ή)-one

Following the procedure as described in Example 6, and performing an insignificant change, using 4-(azepine-based)-2-[4-(trifluoromethyl)phenyl]-1,3-, pyrazole 5-oxyl-3-(a gas-indenyl)-1,2,4-ρ-s-diazole, and using acetone as a solvent to obtain ι'_({2-[4-(trifluoromethyl)phenyl) ]-1,3-pyrazol-4-yl}methyl) snail [pyrano[2,3-f][l,3]benzene® dioxolane-7,3·,哚]- 2'(1Ή)-鲷(36%), as colorless solid: mp 151-153 〇 C; 1H NMR (300 MHz, CDC13) δ 8.02 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.2 Hz, 2H), 7.30-7.21 (m, 2H), 7.17 (d, J = 7.2 Hz, 1H), 7.09-7.00 (m, 2H), 6.51 (s, 1H), 6.18 (s, 1H), 5.85 (s, 2H), 5.13 (ABq, 2H), 4.83 (ABq, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.4, 166.8, 155.9, 152.5, 148.9, 142.3, 141.9, 136.4, 132.2, 131.7 ( q, J = 32.6 Hz), 128.9, 126.7, 126.0 (q, J = 3.7 Hz), 125.7, 123.9, 123.6, 122.1, 119.5, 117.0, 109.5, 103.1, 101.5, 93.7, 80.3, 58.3, 40.4; MS ( ES+) m/z 523.4 (M + 1). 143924-sp-20091127-3 -575- 201020257 Example 6.6

According to the procedure as described in Example 6 and the insignificant change was made, 2-(a)methyl--5-phenyl-1,3,4-,diazole was used to replace the 5-gas group. Methyl)-1,2,4-pyrimidine, and using 2-butanone as a solvent to obtain phenyl hydrazine -1,3,4-indolyldis-2-yl)methyl] snail And [2,3-f][l,3]benzodioxanthene-7,3'-indole-2'(1'11)-one (76%), as a colorless solid: melting point 151 -153. (:; melting point 158-160 〇C; !H NMR (300 MHz, CDC13) ά 8.02-7.94 (m, 2H), 7.56-7.41 (m, 3H), 7.27 (dd, J = 7.5, 7.5 Hz, 1H ), 7.18 (d, J = 7.8 Hz, 1H), 7.06 (d, J = 7.5, 7.5 Hz, 1H), 7.04 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.20 (s , 1H), 5.85 (s, 2H), 5.26 (ABq, 2H), 4.83 (ABq, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.3, 165.8, 161.0, 155.9, 149.1, 142.5, 140.8, 132.1, 131.8, 129.3, 129.2, 127.0, 124.2, 124.1, 123.3, 119.1, 109.0, 103.1, 101.6, 93.7, 80.2, 58.2, ® 35.1; MS (ES+) m/z 440.3 (M + 1). Example 6.7 l'_ {[5_(4_Chlorophenyl)-1,3,4′′diazol-2-yl]methyl}spiro[pf-rano[2,3-f][l,3]benzodiox Synthesis of Wollenene-7,3'-Key 哚]-2'(1Ή)-ketone

• 576- 143924-sp-20091127-3 (8) 201020257 2-(Chloromethyl)-5-(4-phenylphenyl)-1 was used according to the procedure described in Example 6 and with irrelevant changes. , 3,4-oxadiazole was substituted for 5-a gas-3-(alkylmethyl)-l,2,4-p-soxadiazole' and 2-butanone was used as a solvent to obtain ι,_{[5 -(4-chlorophenyl H,3,4-oxadiazol-2-yl]indolyl} snail [bito-and-[2,3-f][l,3]benzodioxolene-7 , 34哚]-2, (1Ή)-one (72%), as colorless solid: mp 161·162 °C; 1H NMR (300 MHz, CDC13) 5 7.91 (d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.5 Hz, 2H), 7.27 (dd, J = 7.7, 7.7 Hz, 1H), 7.19 (d, J = 7.4 Hz, 1H), 7.07 (d, J = 7.5, 7.5 Hz, 1H) , 7.04 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.17 (s, 1H), 5.85 (s, ® 2H), 5.25 (ABq, 2H), 4.82 (ABq, 2H) ; 13C NMR (75 MHz, CDC13) 5 177.3, 165.0, 161.2, 155.9, 149.1, 142.5, 140.7, 138.4, 131.8, 129.6, 129.3, 128.3, 124.3, 124.2, 121.7, 119.1, 109.0, 103.0, 101.6, 93.7, 80.2, 58.2, 35.0; MS (ES+) m/z 474.2 (M + 1), 476.2 (M + 1). Example 6.8 Γ-([1,3 oxazolo[4,5-b]pyridin-2-yl Synthesis of snail [吱,[2,3-f][l,3]benzodioxene-7,3·-吲哚]-2'(1Ή)-net

2-(Chloromethyl)[1,3]carbazolo[4,5-b]pyridine was substituted for 5-alkyl-3 according to the procedure as described in Example 6 except for insignificant changes. -(Alkylmethyl)-1'2,4-pyrimidine" and using 2-butanone as a solvent to obtain a ^^, nickname. Sit and [4,5-noisy bite-2-ylmethyl) snail [吱 并 and yang yang (3) benzodioxosylylene-7,3' 哚] ']-2' (1':«) - Ketone (11%) as a colorless solid: m.p. (:;1111^111 (300 MHz, CDC13) δ 8.56 (d, J = 4.9 Hz, 1H), 7.81 (d, J = 8.2 Hz, 1H), 143924-sp-20091127-3 -577- 201020257 7.34- 7.16 (m, 3H), 7.06 (dd, J = 7.5, 7.5 Hz, 1H), 6.98 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.28 (s, 1H), 5.86 (d , J = 3.6 Hz, 2H), 5.30 (ABq, 2H), 4.85 (ABq, 2H) ; 13C NMR (75 MHz, CDC13) δ 117.4, 163.3, 155.9, 155.0, 149.1, 146.9, 143.4, 142.4, 141.0, 131.9, 129.2, 127.8, 124.1, 120.7, 119.2, 118.8, 109.0, 1033, 101.6, 93.6, 80.4, 58.3, 38.0; MS (ES+) m/z 414.3 (M + 1). Example 7 Γ-(4-A Synthesis of oxybenzyl)spiro[吱,[2,3-f][l,3]benzodioxol-7,3·-啕哚]-2'(1Ή)-one

Snail [snotic [2,3-f][l,3]benzodioxol-7,3'-吲哚]-2'(1Ή)-one (1.99 g, 7.08 mmol) ), 4-methoxy gasified hydrazine (1.30 ml, 9.6 mmol), potassium iodide (0.17 g, 0.99 mmol) and carbonated planer (4.68 g, 14.4 mmol) in 2-butanone (45 ml) The mixture was stirred under reflux for 16 hours under nitrogen. The reaction was cooled, diluted with ethyl acetate and filtered over EtOAc. The filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography eluting with hexane/ethyl acetate (4:1) to afford 1'- (4-methoxybenzyl) snail.吱°南和[2,3-f][l,3]benzodioxene-7,3'-吲嗓]-2, (ΓΗ)-嗣 (2.52 g, 89%), colorless Solid: 147-148°C (hexane); 1H NMR (300 MHz, CDC13) (5 7.28 (d, J = 8.7 Hz, 2H), 7.21 (ddd, J = 7.8, 7.5, 1.2 Hz, 1H) , 7.16 (dd, J = 7.5, 0.6 Hz, 1H), 7.02 (ddd, J = 7.7, 7.4, 1.0 Hz, 1H), 6.88 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.13 (s, 1H), 5.88 (d, J = 1.2 143924*sp-20091127-3 -578 - 201020257

Hz, 1H), 5.87 (d, J = 1.2 Hz, 1H), 5.02 (d, J = 15.3 Hz, 1H), 4.97 (d, J = 9.0 Hz, 1H), 4.76 (d, J = 15.3 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 3.79 (s, 3H); MS (ES+) m/z 402.2 (M + 1) ° Example 7.1 Γ-[3-(trifluoromethyl)benzyl ]]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2,(1Ή)-one Synthesis

According to the procedure as described in Example 7, and irrelevant changes were made, 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8 was used. ,3,-吲哚]-2'(1Ή)-ketone-substituted snail [吱,[2,3-f][l,3]benzodioxene-7,3,-吲哚]- 2'(1Ή)-ketone' and gasification of benzyl with 3-methoxy group by 3-(trifluoromethyl) gasification to obtain hydrazine-[3-(trifluoromethyl)indenyl]-2,3 - Dihydrospiro[吱,[2,3-g][l,4] stupid and oxime oxetene-8 吲哚]-2'(1Ή)-one (92%), as a colorless solid: Melting point 131-134 ° C (ether / hexane); β NMR (300 MHz, CDC13) 6 7.62-7.43 (m, 4 Η), 7.25-7.18 (m, 2H), 7.05 (dd, J = 7.5, 7.5 Hz , 1H), 6.75 (d, J = 7.5 Hz, 1H), 6.52 (s, 1H), 6.23 (s, 1H), 5.14 (d, J = 15.9 Hz, 1H), 4.95 (d, J = 9.0 Hz , 1H), 4.88 (d, J = 15.9 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.23-4.18 (m, 2H), 4.15-4.11 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.8, 155.4, 144.8, 141.8, 138.5, 137.0, 132.3, 131.4 (q, J = 32.4 Hz), 130.7, 129.7, 129.0, 124.9 (q, J = 3.7 Hz), 124.25, 124.22 (q , J = 3.7 Hz), 124.0 (q, J = 272 .4 Hz), 123.8, 120.9, 111.6, 109.1, 99.6, 80.2, 64.7, 64.0, 58.2, 43.8; MS (ES+) m/z 453.9 143924-sp-20091127-3 -579- 201020257 (Μ+l). Example 7.2 5-[(2-keto-2,3-dihydrospiro[2,3_g][1,4]benzodioxene _8,3,_ 吲哚]-Γ Synthesis of (2Ή)-yl) fluorenyl;|pyrene-2-carboxylic acid methyl ester

According to the procedure as described in Example 7, and the insignificant change was made, 2,3-dihydrospiro [bito-benzodioxanthene _8 3, ❹ ❹ 嗓]-2' (1 Ή) was used. -ketone-substituted snail [唉,[2,3_叩,3]benzodioxanthene-7,3,_吲嗓]-2丫1Ή)-one, and 5-(methylmethyl) Substituting methyl 2-furancarboxylate for 4-methoxy gasification of benzyl to give 5-[(2'-keto-2,3-dihydrospiro[2,3-g][l, 4] Methyl benzodioxolene-8,3'-吲哚Η'(2Ή)-yl)methyl]nonan-2-carboxylate (92%), colorless solid: mp 88-92 °C (hexane/diethyl ether); 1H NMR (300 MHz, CDC13) (5 7.28 (ddd, J = 7.8, 7.5, 1.2 Hz, 1H), 7.17 (dd, J = 7.2, 0.9 Hz, 1H), 7.12 (d, J = 3.6 Hz, 1H), 7.06 (ddd, J = 7.8, 7.8, 0.9 Hz, 1H), 6.96 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.37 (d, J = 3.6 Hz, 1H), 6.24 (s, 1H), 5.12 (d, J = 16.5 ® Hz, 1H), 4.91 (d, J = 9.0 Hz, 1H), 4.90 (d, J = 16.5 Hz, 1H ), 4.64 (d, J = 9.0 Hz, 1H), 4.22-4.18 (m, 2H), 4.14-4.10 (m, 2H), 3.89 (s, 3H) ; 1 3 C NMR (75 MHz, CDC13) &lt;;5 177.2, 158.9, 155.3, 153.4, 144.8, 144.4, 141. 4, 138.4, 132.2, 129.1, 124.1, 123.9, 120.9, 119.1, 111.7, 110.3, 109.1, 99.5, 80.1, 64.6, 64.0, 58.1, 52.1, 37.4; MS (ES+) m/z 433.9 (M + 1). Example 7.3 (S)-l'-pentyl-2,3-dihydrospiro [bito-[2,3-g][l,4]benzodioxanene-8,3·- 143924- Sp-20091127-3 • 580- (S) 201020257 吲哚]-2'(1Ή)-ketone synthesis

(3)-2,3_Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-吲嗓]-2'(1Ή)-one (1.0 g, 3.4 mmol), carbonic acid planer (3.3 g, 10.2 mmol) and 1-bromopentane (1.02 g, 6.77 mmol) in anhydrous 1,4-dioxane (25 m The suspension in ® liters was heated under reflux for 2 hours under nitrogen. The reaction mixture was cooled to ambient temperature &apos; filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a gradient of 15% to 50% of ethyl acetate in hexane, followed by recrystallization from methanol to give (5)-1·-pentyl-2,3-dihydrol. Snail [Miso-[2,3-g][l,4]benzodioxanthene-8,3·-峋哚]-2'(1Ή)-_, as an off-white solid (0.89 g' 72 %): melting point 111-113. (:(ethyl acetate/hexane); WNMROOO MHz, CDC13) δ 7.23-7.30 (m, 1H), 7.13 (dd, J = 7.4, 0.9 Hz, 1H), 7.00-7.03 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.46 (s, 1H), 6.19 (s, 1H), 4.73 (ABq, 2H), 4.19-4.05 (m, 4H), 3.86-3.59 (m, 2H), </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; 132.5, 128.7, 123.9, 123.0, 121.1, 111.4, 108.5, 99.3, 80.1, 64.5, 63.9, 58.0, 40.3, 29.0, 27.1, 22.3, 14.0; MS (ES+) m/z 366.0 (M + 1). Example 7.4 Late)-1|-pentyl-2,3-dihydrospiro[吱,[2,31][1,4]benzodioxanthene-8,3'-呻哚]-2Χ1Ή )-keto synthesis 143924-sp-20091127-3 -581 - 201020257

According to the procedure as described in Example 7.3, and with irrelevant changes, use (R)-2,3-dihydrospiro[吱,[2,3 g][1,4]benzodioxan Dilute _8,34 % ]-2(1 H)-ketone replacement (5)_2,3-dihydrospiro[吱3[g]g[1,4]benzodioxanthene_8,3'_吲哚]_2,(1Ή)-ketone, obtain (8)-factor pentyl 2,3_dihydrospiro[furo[2'3-g][l'4]benzodioxanthene_8,3 , _, 哚]_2, (1Ή) ketone (74%), as a colorless solid: 4 NMR (300 MHz, CDC13) (5 7.25-7.30 (m, 1 Η), 7.16-7.11 (m, 1H), 6.99- 7.04 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.47 (s, 1H), 6.19 (s, 1H), 4.73 (ABq, 2H), 4.20-4.06 (m, 4H), 3.86 -3.59 (m, 2H), 1.82-1.63 (m, 2H), 1.42-1.28 (m, 4H), 0.89 (t, J = 6.8 Hz, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.2, 155.2, 144.5, 142.4, 138.2, 132.5, 128.7, 123.9, 123.0, 121.2, 111.4, 108.5, 99.3, 80.1, 64.5, 63.9, 58.0, 40.3, 29.0, 27.1, 22.3, 14.0; MS (ES+) m/z 366.1 (M+ 1) Example 7.5 Γ-Hexyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzoindene ruthenium-8,3'-啕哚]- Synthesis of 2'(1Ή)-ketone

143924-sp-20091127-3 -582- 201020257 Follow the procedure as described in Example 7.3, and perform irrelevant changes using 2,3-dihydrospiro[?,[2,3-^14] benzo Dioxetemene_8&gt;3ι_吲哚]_ 2'(1Ή)-ketone replacement (3)-2,3-dihydrospiro[,4,3_g][1,4]benzodioxan Terpene-8,3·'嗓]-2'(1Ή)-, and replacing g-pentane with μ-bromohexane to obtain Γ-hexyl-2,3-dihydrospiro[吱吱[2 , 3-g][1,4]benzodioxanthene _8,3,吲嗓]-2'(1Ή)-one (83%), as a colorless solid: iH (3〇〇CDCl3) 7.25-7.29 (dt, J = 7.74, 7.71, 1.05 Hz, 1H), 7.13 (d, J = 7.4 Hz, 1H), 6.98-7.04 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H) , 6.46 (s, 1H), 6.19 (s, 1H), 4.73 (ABq, 2H), _ 4.19-4.05 (m, 4H), 3.86-3.59 (m, 2H), 1.80-1.63 (m, 2H), 1.44-1.22 (m, 6H), 0.87 (t, J = 6.9 Hz, 3H); 13 C NMR (75 MHz, CDC13) δ 112, 155.2, 144.5, 142.4, 138.2, 132.5, 128.7, 123.9, 123.0, 121.2 , 111.4, 108.5, 99.3, 80.1, 64.5, 63.9, 58.0, 40, 3, 31.4, 27.4, 26.5, 22.5, 14.0; MS (ES+) m/z 379.9 (M + 1). Example 7.6 1·-(2-cyclopropylethyl)-2,3-dihydrospiro[吱,[2,3-g][l,3]benzodioxanthene-8,3· -啕哚]·2'(1Ή)-ketone synthesis

According to the procedure as described in Example 7.3, and irrelevant changes were made, 2'3-dihydrospiro[吱-benzodioxanthene _8,3,吲哚&gt; 2' (1Ή) was used. -ketone replacement (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8'3W丨哚]-2' (1' H)-ketone, and the use of 4_mercaptobenzenesulfonic acid 2_cyclopropylethyl ester to replace 1-methyl pentane' to obtain 1'-(2_cyclopropylethyl)_2,3_dihydrospiro Fudan[2,3_g] 143924-sp-20091127-3 -583 - 201020257 [1,3]benzoxantheneene-8,3'-啕哚]-2·(1Ή)-one (59 %), as a colorless solid: 1H NMR (300 MHz, CDC13) δ 7.12 (d, J = 7.4 Hz, 2H), 6.96-7.04 (m, 1H), 6.90 (d, J = 7.8 Hz, 1H), 6.45 (s, 1H), 6.19 (s, 1H), 4.72 (ABq, 2H), 4.19-4.03 (m, 4H), 3.94-3.71 (m, 2H), 0.79-0.64 (m, 1H), 0.50-0.37 (m, 2H), 0.11-0.04 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 177.2, 155.2, 144.5, 142.6, 138.2, 132.4, 128.7, 123.9, 123.0, 121.1, 111.5, 108.5, 99.3 , 80.1, 64.5, 63.9, 57.9, 40.4, 32.4, 8.6, 4.4; MS (ES+) m/z 364.0 (M + 1). Example 7.7 1·-(2-ethoxyethyl)-2,3-dihydrospiro[吱,[2,3-g][l,3]benzodioxanthene-ene-8,3 '-吲哚]-2'(1Ή)-the synthesis of the class

According to the procedure as described in Example 7.3, and the insignificant changes were made, 2,3-dihydrospiro [c-buto[2,3-g][l,4]benzodioxene _8 was used. ,3,_嘀哚]-2'(1Ή)-ketone substitution, ie,-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene- 8,3M丨哚]-2'(1Ή)-ketone' and substituting 1-bromopentane with 1-bromo-2-ethoxyethane to obtain Γ-(2-ethoxyethyl)-2 ,3-dihydrospiro [bito-and-[2,3-g][l,3]benzodioxanthene -8,3'-noise]-2'(1Ή)-ketone (50%) , as a colorless solid: 1H NMR (300 MHz, CDC13) δ Ί 31-7.21 (m, 1 Η), 7.14-7.09 (m, 1H), 7.07-6.97 (m, 2H), 6.46 (s, 1H), 6.21 ( s, 1H), 4.74 (ABq, 2H), 4.19-4.05 (m, 4H), 4.03-3.80 (m, 2H), 3.74-3.61 (m, 2H), 3.49 (q, J = 7.0 Hz, 2H) , 1.14 (t, J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDC13) &lt;5 177.5, 155.1, 144.5, 142.6, 138.2, 143924-sp-20091127-3 - 584- (s) 201020257 132.3, 128.6, 123.6, 123.1, 121.2, 111.5, 109.2, 99.2, 80.0, 67.4, 66.6, 64.5, 63.9, 57.9, 40.4, 15.1; MS (ES+) m/z 368.1 (Μ + 1). Example 7.8 Γ-(4-methoxybutyl)-2,3-dihydrospiro[N-[2,3-g][l,3]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 7.3, and irrelevant changes were made, 2,3-dihydrospiro[p,pyrano[2,3-g][l,4]benzodioxanthene- 8,3,-吲哚]-2'(1Ή)-keto-substituted 〇2,3-dihydrospiro[sn-[2,3-g][l,4]benzodioxanthene-8 , 3W丨哚]1(1Ή)-ketone, and 1--(4-methoxybutyl)-2,3-, obtained by substituting μ-bromo-4-butoxybutane for 1-bromopentane Dihydrospiro[吱,[2,3-g][l,3]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one (93%), colorless Solid: β NMR 300 (300 MHz, CDC13) 6 7.30-6.86 (m, 4 Η), 6.45 (s, 1 Η), 6.18 (s, 1 Η), 4.72 (ABq, 2H), 4.18-4.04 (m, 4H) , 3.88-3.63 (m, 2H), 3.44-3.37 (m, 2H), 3.30 (s, 3H), 1.88-1.56 (m, 4H); 13 C NMR (75 MHz, CDC13) δ 177.2, 155.2, 144.5 , 142.3, 138.2, 132.5, 128.8, 123.9, 123.1, 121.1, 111.4, 108.6, 99.3, 80.1, 72.0, 64.5, 63, 9, 58.6, 57.9, 40.0, 26.9, 24·3; MS (ES+) m/z 381.9 (M+l). Example 7.9 1K3-methoxypropyl)-2,3-dihydrospiro[吱,[2,3-g][l,3]benzodioxanthene-8,3W丨哚]-2 Synthesis of '(1Ή)-ketone 143924-sp-20091127-3 •585· 201020257

According to the procedure as described in Example 7.3, and with irrelevant changes, use 2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxolene-8 ,3,_4丨哚]_ 2(1 H)-ketone replacement (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,3'-(9)嗓]-2·(ΓΗ)-net' and the replacement of 1 -(3-methoxypropyl) with 1_bromo methoxypropane 2,3-Dihydrospiro[Vfu and [2,3_g][i,3]benzodioxanthene-8,3'-啕哚]-2,(1,H)-one (71 %) as a colorless solid: iH NMR (300 MHz, CDC13) δ 7.30-6.93 (m, 4 Η), 6.46 (s, 1H), 6.18 (s, 1H), 4.72 (ABq, 2H), 4.19-4.04 ( m, 4H), 3.94-3.72 (m, 2H), 3.41 (t, J = 5.9 Hz, 2H), 3.30 (s, 3H), 2.01-1.91 (m, 2H) ; NMR (75 MHz, CDC13) &lt;;5 177.3, 155.2, 144.5, 142.5, 138.2, 132.4, 128.8, 123.8, 123.1, 121.1, 111.4, 108.5, 99.3, 80.0, 69.7, 64.5, 63.9, 58.7, 57.9, 37.6, 27.8; MS (ES+) m/ z 367.9 (M + example 7.10 1'-(3-nitroindenyl)-2,3-dihydrospiro [biting and [23_illus [1,3] stupid and dioxane terpene mP]- 2, (1Ή)-ketone synthesis

Follow the procedure as described in Example 7.3 and perform irrelevant changes, 143924-sp-2009U27-3 * 586 - 201020257 using 2,3-dihydrospiro [furo[2,3-g][l,4 Benzenedioxene terpene-8,3·-啕哚]-2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro[吱喃 P,3-g][l, 4] benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one, and 1-bromopentane substituted with 1-(bromomethyl)-3-ylbenzene , obtaining Γ-(3-nitrobenzyl)-2,3-dihydrospiro[olleno[2,3-g][l,3]benzodioxanthene-8,3W丨哚] - ΑΓΗ)-ketone (72%) as colorless solid: iHNMRQOO MHz, CDC13) δ 8.19 (s, 1H), 8.12 (d, J = 8.1 Hz, 1H), 7.77 (d, J = 7.7 Hz, 1H) , 7.60-7.66 (m, 1H), 7.28-6.97 (m, 4H), 6.49 (s, 1H), 6.13 (s, 1H), 5.07 (ABq, 2H), 4.73 (ABq, 2H), 4.18-4.03 (m, 4H) ; 13C NMR (75 MHz, ❹ CDC13) 5 177.4, 155.2, 148.4, 144.7, 142.3, 139.1, 138.3, 134.2, 132.1, 130.8, 129.3, 124.2, 123.7, 122.9, 122.3, 121.5, 111.5, 109.8, 99, 3, 79.9, 64.6, 64.0, 57.7, 42.8; MS (ES+) m/z 430.9 (M + 1). Example 7.11 Γ-(1,3-pyrazol-5-ylindenyl)-2,3-dihydrospiro[吱,[2,3-g][l,3]benzodioxanthene- Synthesis of 8,3'-choline]-2'(1Ή)-ketone

Follow the procedure as described in Example 7.3 and perform irrelevant changes,

Replacement of (S)-2,3- using 2'3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene]-2'(1Ή)-one Di-argon snail [吱,[2,3-g][l,4]benzodioxanthene-8,3W|哚]-2*(1Ή)-ketone' and use 5-(chloromethyl) Substituting thiazole for the replacement of μ bromopentane' to obtain Γ-(1,3-oxazosin-5-ylindenyl)-2,3-dihydrospiro[,,[2,3-g][l, 3] benzodioxanthene-8,3'-anthole]-2'(1Ή)-one (56%) as a colorless solid: 1h NMR 143924-sp-20091127-3 -587- 201020257

(300 MHz, CDC13) δ 8.72 (s, 1H), 7.89 (s, 1H), 7.29-6.86 (m, 4H), 6.47 (d, J = 2.0 Hz, 1H), 6.16 (d, J = 2.0 Hz) , 1H), 5.13 (ABq, 2H), 4.74 (ABq, 2H), 4.20-4.03 (m, 4H); 13C NMR (75 MHz, CDC13) &lt;5 177.0, 155.2, 153.8, 144.7, 142.6, 141.0, 138.3, 133.0, 132.2, 128.9, 124.1, 123.8, 120.7, 111.5, 108.7, 99.4, 79.9, 64.5, 63.9, 57.9, 36, 2; MS (ES+) m/z 392.4 (M + 1). Example 7.12 Γ-{[5-(Trifluoromethyl oxaridin-2-yl)methyl}-2,3-dihydrospiro[, succinyl[2,3-g][l,3] benzodiazepine Synthesis of oxetene-8,3%?丨哚]-2'(1 Ή)-ketone

2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 was used according to the procedure described in Example 7.3, and irrelevant changes were applied. ,3,-W 哚]-ΑΓΗ)-ketone replacement (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8, 3'-吲哚]-2'(1Ή)-one, and 1-(bromomethyl)-5-(trifluoromethyl)pyridine was substituted for 1-bromopentane to obtain Γ-{[5- (Trifluoromethyl oxaridin-2-yl)methyl}-2,3-dihydrospiro[吱,[2,3-g][l,3] benzodioxanthene-8,3 '-W哚]-2'(1Ή)-ketone (53%) as colorless solid: 4 NMR (300 MHz, CDC13) 5 8.83 (s,1Η), 7.89 (dd, J = 8.2, 2.0 Hz, 1H ), 7.42-6.81 (m, 5H), 6.50 (s, 1H), 6.28 (s, 1H), 5.13 (ABq, 2H), 4.80 (ABq, 2H), 4.22-4.07 (m, 4H) ; 1 3C NMR (75 MHz, CDCI3) &lt;5 177.6, 159.4, 155.2, 146.5, 146.5, 144.7, 141.7, 138.3, 134.3, 134.3, 134.2, 132.1, 128.9, 126.1, 125.6, 125.1, 124.0, 123.7, 121.4, 120.8, 111.6, 109.2, 99.4, 80.0, 64.5, 63.9, 58.1, 45.7; MS (ES+) m/z 454.9 (M + 1). 143924-sp-20091127-3 •588· 201020257 Example 7.13 Γ-{[3-( Trifluoromethyl &gt;Bipyridin-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l,3] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 7.3, and irrelevant changes were made, 2 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene terpene was used.哚]-2·(1Ή)-_substitution of (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3' -(9)哚]-Τ(1Ή)-_, and using 2-(chloromethyl)-3-(trifluoromethyl)&gt;-pyridyl hydrochloride to replace 1-bromopentane to obtain Γ-{[ 3-(Trifluoromethyl)acridin-2-yl]methyl}-2,3-dihydrospiro[Homo-[2,3-g][l,3]benzodioxanthene- 8,3'-啕哚]-2Χ1Ή)-ketone (40%), as a colorless solid: 1H NMR (300 MHz, CDC13), 8.62 (d, J = 4.7)

Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.32-6.96 (m, 4H), 6.71-6.54 (m, 2H), 6.48 (s, 1H), 5.22-5.28 (m, 2H) , 4.80-4.90 (m, 2H), 4.21-4.06 (m, 4H) ; 13 C NMR _ (75 MHz, CDC13) δ 178.1, 155.1, 152.3, 144.5, 142.3, 138.2, 134.3, 134.2, 134.1, 134.1, 132.7, 129.2, 128.6, 125.6, 124.9, 124.5, 124.1, 123.8, 123.6, 123.2, 122.1, 122.0, 121.6, 112.4, 108.5, 99.1, 80.0, 64.5, 63.9, 58.2, 42.2, 42.2; MS (ES+) m/ z 454.8 (M + 1). Example 7.14 Γ-[(3-Pyridin-3-ylisoxazol-5-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,3] benzo Synthesis of Dioxinol-8,3'-峋哚]-2·(1Ή)-ketone 143924-SP-20091127-3 •589· 201020257

According to the procedure as described in Example 7.3, and with irrelevant changes, use 2,3-dihydrospiro [biting and [2,3 g] to 4] benzodioxene _8 3, _β哚2'(1Ή)-ketone replacement (S)-2,3-dihydrospib- succinyl and dioxin-terpene-8,3'-de-supplemented-2'(1Ή)-one, And replacing 5-y-ylpentane with 5_(a gas-based thiol)_3_(p-pyridyl)isoxazole to obtain 丨'you·pyridylisoxazole _5_yl)methyl]_2,3 _瘳Dihydrospiro[吱,[2,3-g][l,3]benzodioxolene-8,3,-吲哚]-2,(1Ή)-one (40%) ' Is a colorless solid: 1 η NMR (3 〇〇 MHz, CDCl3) 8 96 (s, m), 8 65 (Mountain J = 4.7 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.39-6.98 (m, 5H), 6.58 (s, 1H), 6.47 (s, 1H), 6.20 (s, 1H), 5.10 (ABq, 2H), 4.76 (ABq, 2H), 4.20-4.03 (m, 4H); 13C NMR (75 MHz, CDC13) (5 177.2, 167.7, 160.3, 155.2, 151.2, 147.9, 144.7, 141.0, 138.3, 134.0, 131.9, 129.1, 124.7, 124.1, 124.1, 123.7, 120.5, 111.5, 108.8, 100.9, 99.4, 79.9, 64.5, 63.8, 57.9, 35.8; MS (ES+) m/z 453.9 (M + 1). Example 7.15 (8 ft)-1'-{[3-(trifluoro风 啶 -2- 基 基 基 } } } } } } 味 味 味 味 味 味 [2,3_g] [1,3] benzodioxanthene-8,3'_ 哚 哚]- 2·(1Ή)-ketone synthesis

143924-sp-20091127-3 -590- (S) 201020257 According to the procedure described in Examples 7, 3, and with irrelevant changes, use (尺)-2,3-dihydrospiro[吱喃和[ 2,3_g][1,4]benzodioxanthene _8,3,_p?丨嗓]-2'(1Ή)-嗣 replacement (3)_2,3_dihydrospiro[furo[2,3 g [14] benzodioxanthene-8,3'-4丨嗓]-2'(1Ή)-one' and 2-(chloromethyl)-3-(trifluoromethyl)pyridine Hydrochloride substitution of 1-bromodecane' afforded (trifluoromethylpyridin-2-yl)methyl}-2,3-dihydrospiro-I; indolo[2 3_g][1,3]benzene Dioxetemene _8,3,_ 哚 哚]-2 (1 H)-one (72%) as a colorless solid: 1H NMR (3 〇〇MHz, CDCl3)

δ 8.63 (d, J = 4.5 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.34-6.96 (m, 4H), 6.62 (s, 1H), 6.59 (d, J = 7.8 Hz, 1H), 6.48 (s, 1H), 5.26 (ABq, 2H), 4.85 (,2H), 4.21-4.08 (m,4H) ; &quot;c NMR (75 MHz, CD%) for i78 i, i55 i, I523, 144.5' 142.3, 138.2, 134.3, 134.2, 134.1, 134.0, 132.7, 128.5, 125.6, 124.9, 124.5, 124.1, 123.8, 123.2, 122.1, 122.0, 121.6, 112.4, 108.5, 99.1, 80.0, 64.5, 63.9, 58.2, 42.2, 42.2; MS (ES+) m/z 454.8 (M + 1). Example 7.16 N,N-monomethyl-3-[(2'-keto-2,3-dihydrospiro[[2,3_g][14] stupid and dioxo-salt-83,4 Synthesis of 丨嗓&gt;Γ-(2Ή)-yl)methyl]benzenesulfonamide

According to the procedure described in Example 7.3, and the irrelevant changes were made, 2,3-dihydrospiro [Miso[2,3liu,4]benzodioxanthene _8,3 was used. , 2 (1 Η)-ketone replacement (S)-2,3-dihydro snail [bite suffix [such as (10) benzotrioxide terroir 143924-sp-20091127-4 -591· 201020257 -8, 3·-〃5丨哚]-2(1Ή)-ketone, and replacing 3-bromopentane with 3-(azepine)-N,N-diphenylbenzenesulfonamide to obtain N,N- Dimercapto-3-[(T-keto-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-Γ-(2Ή)-yl)methyl]benzenesulfonamide (40%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ 7.72-7.62 (m, 4 Η), 7.29-6.99 (m, 4H), 6.50 (s, 1H), 6.07 (s, 1H), 5.06 (ABq, 2H), 4.71 (ABq, 2H), 4.19-4.05 (m, 4H), 2.50 (s, 6H); 13C NMR (75 MHz, DMSO-d6) δ 176.9, 154.7, 144.2, 141.9, 137.8, 134.9, 131.8, 131.5, 129.9, 128.8, 126.6, 125.9, 123.8, 123.2, 120.9, 110.9, 109.3, 98.8, 79.4, 64.2 , 63.5, 57.2, 42.5, 37.4; MS (ES+) m/z 492.7 (M + 1). Example 7.17 Γ-[3-(morpholine-4-ylsulfonyl)hanyl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxane Synthesis of terpene-8,3'-啕哚]-2'(1Ή)-ketone

2'3-Dihydrospiro[吱,[2,3-g][i,4]benzodioxene-8 was used according to the procedure described in Example 7.3, and irrelevant changes were applied. ,3,-W哚]-2'(ΓΗ)-ketone replacement (5)_2,3-dihydrospiro [bito-and-[2,3-g][i,4]benzodioxanthene-8'3 '-Bian Duo]-2'(1Ή)-ketone, and 4-(3-(methylmethyl)benzenesulfonyl)porphyrin was substituted for 1-bromopentane to obtain florin sulfonate醯基)竿基]_2,3_Dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene _8,3,_ 哚 哚]_2, (1, Η)-ketone (40%) ' is a colorless solid: iHNMR (3 〇〇 MHz, DMS 〇 _d6) 773 764 (m, 143924-sp-20091127-4 • 592-201020257 4H), 7.29-7.18 (m , 2H), 7.05 (dd, J = 7.3, 5.6 Hz, 2H), 6.52 (s, 1H), 6.11 (s, 1H), 5.09 (ABq, 2H), 4.74 (dd, J = 9.3 Hz, 2H) , 4.04-4.21 (m, 4H), 3.56 (t, J = 4.5 Hz, 4H), 2.84-2.65 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) &lt;5 176.9, 154.8, 144.2 , 141.9, 138.0, 137.9, 134.7, 132.2, 131.6, 130.1, 128.8, 126.7, 125.9, 123.9, 123.3, 121.0, 110.9, 109.5, 98.9, 79.5, 65.2, 64.2, 63.6, 57.3, 45.8, 42.5; MS (ES +) m/z 534,9 (M + 1). Example 7.18 14(4-Mercapto-1,2,5-soxadiazol-3-yl)indolyl]-2,3-dihydrospiro[?,[2,3-g][l,4 Synthesis of benzodioxanthene _8,3'-吲哚]-2·(1Ή)-_

2,3-Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8 was used according to the procedure described in Example 7.3, and irrelevant changes were applied. 3,^引哚]-2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan φ decene -8,3'-啕哚]-2'(1Ή)-one, and 3-(chloromethyl)-4-methyl-1,2,5-唠

Diazole is substituted for 1-bromopentane to obtain 1,-[(4-mercapto-1,2,5-oxadiazol-3-yl)indenyl]-2,3-dihydrospiro[furan[ 2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2·(anthracene)-one (69%) as a colorless solid: iHNMR (300MHz, DMSO- D6) δ 7.36-7.28 (m, 1H), 7.22-7.03 (m, 3H), 6.52 (s, 1H), 6.23 (s, 1H), 5.19 (ABq, 2H), 4.73 (ABq, 2H), 4.22 -4.07 (m, 4H), 2.41 (s, 3H); 13 C NMR (75 MHz, DMSO-d6) δ 176.6, 154.6, 151.4, 151.3, 144.2, 141.6, 137.8, 131.8, 128.7, 123.6, 123.4, 121.1 , 111.2, 109.3, 98.7, 79.3, 64.2, 63.6, 57.2; MS 143924-sp-20091127-4 -593 - 201020257 (ES+) m/z 414.0 (M + 23). Example 7.19 Γ-(2,3-Difluoroindolyl)-2,3-dihydrospiro[1,3-g][l,4]benzodioxanthene _8,3' -吲哚]-2\1Ή)-the synthesis of ketone

2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 was used according to the procedure described in Example 7.3, and irrelevant changes were applied. , 3'-chao哚]_ 2'(1Ή)-ketone replacement (5)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 , 3·-吲多]-2·(1Ή)-ketone' and the use of 1_(bromohydrazino)_2,3_difluorobenzene to replace 1_xiylpentane' to obtain Γ-(2,3-difluoro芊))-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8,3'-啕哚]-2' (1 ugly) -ketone (47%) as a colorless solid: 11^1^ (300 MHz, DMSO-d6) δ 7.45-7.10 (m, 5H), 7.01-7.08 (m, 1H), 6.99 (d, J = 7.8 Hz , 1H), 6.52 (s, 1H), 6.14 (s, 1H), 5.04 (ABq, 2H), 4.74 (ABq, 2H), 4.22-4.06 (m, 4H) ; 13 C NMR (75 MHz, DMSO- De) 5 176.6, 154.7, 144.2, 141.9, 137.8, 131.6, 128.9, 125.7, 125.6, 125.2, 124.4, 123.7, 123.2, 121.0, 116.9, 116.7, 111.1, 109.1, 98.8, 79.5, 64.2, 63.6, 57.2; (ES+) m/z 421.8 (M+l). Example 7.20 1'-(3,5-Difluorobenzyl)-2,3-dioxaspiro[吱,[2,3-g][l,4]benzodioxanthene-8,3 Synthesis of '-吲哚]-2'(1Ή)-ketone 143924-sp-20091127-4 -594« 201020257

According to the procedure as described in Example 7.3, and with irrelevant changes, 2,3-dihydrospiro[吱,[2,3$][1,4]benzodioxene-8 was used. 3'-吲哚]-2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3·-啕哚]-2'(1Ή)-_, and 1-(bromodecyl)-3,5-difluorobenzene substituted 1-bromoφ-pentane' to obtain l'-(3 ,5-difluorobenzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3'_吲哚]-2 · (1Ή)-ketone (72%) as a colorless solid: iHNMR (300 MHz, DMSO-d6) δ 7.22-7.32 (m, 1 Η), 7.24-7.14 (m, 2H), 7.13-7.00 (m, 4H ), 6.53 (s, 1H), 6.11 (s, 1H), 4.96 (s, 2H), 4.77 (ABq, 2H), 4.23-4.07 (m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.6, 154.7, 144.2, 141.9, 137.8, 131.6, 128.9, 125.7, 125.6, 125.2, 124.4, 123.7, 123.2, 121.0, 116.9, 116.7, 111.1, 109.1, 98.8, 79.5, 64.2, 63.6, 57.2; MS (ES+) m/z 421.8 (M + 1). ❿Example 7.21 Γ-(4-fluoroaryl)-2,3-dihydrospiro[唉,[2,3_g][1,4]benzodioxanthene-8J-吲哚;μ2ι(1Ή )_·The synthesis

Follow the procedure as described in Example 7.3 and perform an insignificant change' using 2,3-dihydrospiro[唉,[2,3_g][l,4]benzodioxolene-8,3 ,吲143924-sp-20091127-4 •595· 201020257 哚]-2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro [p-and-[2,3-g][l, 4] benzodioxanthene-8,3'-嘀哚]-2Χ1Ή)-ketone' and the use of ι_(molylmethyl)_4_fluorobenzene to replace 1-bromopentane' to obtain Γ-( 4-fluoroindolyl-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxolene-8,3'-啕哚]-2乂1Ή )-嗣(73%), as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ 7.45-7.37 (m, 2 Η), 7.31-7.23 (m, 1H), 7.23-7.14 (m, 3H), 7.07-6.99 (m, 2H), 6.53 (s, 1H), 6.09 (s, 1H), 4.92 (ABq, 2H), 4.74 (ABq, 2H), 4.22-4.07 (m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.7, 154.7, 144.2, 142.1, 137.8, 132.6, 132.5, 132.0, 129.4, 129.3, 128.8, 123.7, 123.1, 121.2, 115.7, 115.4, 111.0, 109.4, 98.8, 79.4, 64.2, 63.6 , 57.2, 42.4 ; MS (ES+) m/z 403.8 (M + 1). Example 7.22 1'-(2-Acetyl-4-fluorobenzyl)-2,3-dihydrospiro[N,3[3,3][1,4]benzodioxanthene-8, Synthesis of 3^吲哚]-2'(1Ή)-ketone

2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 was used according to the procedure described in Example 7.3, and irrelevant changes were applied. ,3,-吲哚]_ 2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro [snolo[2,3-g][l,4]benzodioxanthene -8,3|-吲哚]-2'(1Ή)-ketone' and replacing 1-bromopentane with 1-(bromomethyl)_2_alkyl-4-fluorobenzene to obtain Γ-( 2-gas-based fluoroaryl)-2,3-dihydrospiro[,,[2,3-g][l,4]benzodioxene-8,3'-啕哚]- 2·(1Ή)-ketone (81%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) 5 7.52-7.60 (m, 1 Η), 7.35-7.17 (m, 143924-sp-20091127-4 - 596- 201020257 4H), 7.10-7.02 (m, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.52 (s, 1H), 6.24 (s, 1H), 4.97 (ABq, 2H), 4.75 ( ABq, 2H), 4.22-4.08 (m, 4H); 1 3 C NMR (75 MHz, DMSO-d6) δ 176.7, 154.8, 144.2, 142.1, 137.8, 132.9, 131.7, 130.1, 129.5, 129.4, 128.9, 123.8 , 123.2, 121.0, 117.2, 116.9, 114.9, 111.3, 109.3, 98.8, 79.6, 64.2, 63.6, 57.2, 41.1; MS (ES+) m/z 437.6 (M+l). Example 7.23 Γ-[(1-Methyl-1H-benzotriazol-5-yl)methyl]-2,3-dihydrospiro[1,3-g][l,4]benzene Synthesis of dioxin terpene _8,3'_啕哚]-2'(1Ή)-one

Follow the procedure as described in Example 7.3 and perform irrelevant changes using 2,3-dihydrospiro[2,3-g][l,4]benzodioxene-8 ,3,-吲哚]-2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene -8,3'-啕哚]-2·(1Ή)-嗣, and using 5-(aeromethyl)-1-methyl-1H-benzo[d] ❿ [1,2,3] Replacement of 1-bromopentane with azole to obtain 1,-[(l-fluorenyl-1H-benzotriazol-5-yl)methyl]-2,3-dihydrospiro[biting and [2,3 -g][l,4]benzodioxanthene-8,3'-indole-2'(1Ή)-one (15%) as a colorless solid: iHNMR (300MHz, DMSO-d6) δ 8.08 (s, 1H), 7.86 (d, J = 8.6 Hz, 1H), 7.52 (dd, J = 8.6, 1.2 Hz, 1H), 7.20-7.28 (m, 1H), 7.18 (d, J = 6.9 Hz , 1H), 7.08 (d, J = 7.7 Hz, 1H), 7.02 (t, J = 7.4 Hz, 1H), 6.54 (s, 1H), 6.08 (s, 1H), 5.10 (ABq, 2H), 4.77 (ABq, 2H), 4.28 (s, 3H), 4.22-4.07 (m, 4H); 13C NMR (75 MHz, DMSO-c^) δ 176.8, 154.7, 145.2, 144.2, 142.0, 137.8, 132.9, 132.4, 131.7, 128.8, 126.7, 123.7, 143924-sp-20091127-4 -597· 201020257 123.1, 121.2, 117.6, 111.3, 110.9, 109.5, 98.9, 79.4, 64.2, 63.6, 57.3, 43.1, 34.2; MS (ES+) m/z 440.9 (Μ + 1). Example 7.24 1'-[(3-Trifluorodecyloxy)-yl]-2,3-di-argon[吱,[2,3-g][l,4]benzodioxanthene- Synthesis of 8,3'-蚓哚]-2,(1Ή)-ketone

According to the procedure as described in Example 7.3, and with irrelevant changes, 2,3-dihydrospiro [snolo[2,3-g][l,4]benzodioxanthene was used in spring. 8,3'-吲哚]-2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Alkene-8,3'-fluorene]-2'(1Ή)-one, and 1-bromopentane is replaced with 1-(indiyl)-3-(trifluoromethoxy)benzene to obtain hydrazine-[ (3-trifluorodecyloxy)octyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3'-(9)哚-2'(1Ή)-one (62%), as a colorless solid: 4 NMR (300 MHz, DMSO-dg) &lt;5 7.47-7.55 (m,1 Η), 7.41-7.34 (m, 2H), 7.33 -7.24 (m, 2H), 7.22-7.17 (m, 1H), 7.09-7.00 (m, 2H),

O 6.53 (s, 1H), 6.08 (s, 1H), 5.00 (ABq, 2H), 4.75 (ABq, 2H), 4.22-4.07 (m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.9 , 154.7, 148.6, 148.5, 144.2, 142.0, 139.3, 137.9, 131.6, 130.8, 128.8, 126.2, 123.7, 123.2, 121.1, 120.1, 120.0 (q, Jc-F= 256.4 Hz), 119.7, 110.9, 109.3, 98.8 , 79.4, 64.2, 63.6, 57.2, 42.5; MS (ES+) m/z 469.9 (M + l). Example 7.25 Γ-[(2-Fluoro-6-trifluoromethyl)-yl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxan Synthesis of terpenes]-2'(1Ή)-ketone-598· 143924-sp-20091127-4 (S) 201020257

According to the procedure as described in Example 7.3, and with irrelevant changes, use 2,3-dihydrospiro[吱,[2,3-g][i,4] benzodioxanthene-8 ,3,_吲哚]-2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro[,,[2,3_g][1,4]benzodioxanthene] -2·(ΓΗ)-ketone' and the replacement of I-bromopentane with 2-(Methylyl)_ι_fluoroyl_3_(trifluoroφmethyl)benzene to obtain 1·-[(2-fluoro group) -6-trifluoromethyl)-yl,-2,3-dihydrospiro[B-pyrano[2,3-g][l,4]benzodioxanthene _8,3'_峋嗓]_2, (1Ή) ketone (68%) as a colorless solid: iHNMRQOOMHz 'DMSO-de) &lt;5 7.73-7.53 (m, 3H), 7.24 (ddd, J = 7.7, 7.7, 1.2 Hz, 1H) , 7.16 (dd, J = 7.3, 0.9 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 6.81 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.14 (s, (H), 4. , 131.7, 130.7, 130.6, 129.4, 129.3, 129.0, 128.7, 125.4, 125.3, 123.7, 123.0, 122.7, 121.7, 〇121.5, 121.0, 120.8, 120.5, 111.2, 108.6, 98.7, 79.6, 64.2, 63.6, 56.9, 3 63 ; MS (ES+) m/z 471.8 (M + 1). Example 7·26 1·-[(2-Fluoro-5-trifluoromethyl)-yl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzo Synthesis of Dioxetine-8,3'-峋哚]-2'(1'11)-one 143924-sp-20091127^ -599- 201020257

2,3-Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8 was used according to the procedure described in Example 7.3, and irrelevant changes were applied. 3,-啕嗓]-2'(1Ή)-net replacement (S)-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene- 8,3·-啕哚]-2·(1Ή)-ketone, and replacing 1-bromopentane with 2-(indiylthio)-difluoro-4-(trifluoromethyl)benzene to obtain hydrazine -[(2-Fluoro-5-trifluoromethyl)hanyl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene- 8,3·-吲哚]-2'(1Ή)-one (75%) as a colorless solid: iHNMR (300MHz, DMSO-d6) 5 7.84-7.76 (m, 1H), 7.75-7.69 (m, 1H ), 7.50-7.55 (m, 1H), 7.26-7.33 (m, 1H), 7.20 (d, J = 6.8 Hz, 1H), 7.10-7.00 (m, 2H), 6.53 (s, 1H), 6.05 ( s, 1H), 5.08 (ABq, 2H), 4.74 (ABq, 2H), 4.22-4.06 (m, 4H); 13C NMR (75 MHz, DMSO-d6) &lt;5 176.7, 164.0, 160.7, 154.7, 144.2 , 141.8, 137.9, 131.6, 128.9, 127.5, 127.47, 127.39, 127.3, 126.9, 126.8, 126.7, 126.2, 126.1, 125.7, 125.6, 125.3, 125.2, 124.8, 124.6, 123.8, 123.7 (q, JC.F = 271.8 Hz), 123.3, 121.1, 117.3, 116.9, 110 .8, 109.1, 98.9, 79.4, 64.2, 63.6, 57.2, 37.7; MS (ES+) m/z 471.8 (M + 1). Example 7.27 Γ-[(2-Trifluoromethoxy)-yl]-2,3-dihydrospiro[M-benzodioxanthene-8,3·-啕哚]-2, (1Ή Synthesis of _ _ 143924-sp-20091127-4 201020257

According to the procedure as described in Example 7.3, and with irrelevant changes, use 2,3-hydrospiro[吱,[2,3-g][i,4]benzodioxene _8 ,3,吲哚]_ 2'(1Ή)-ketone replacement (S)-2,3-dihydrospiro[吱,[2,3-§][1,4]benzodioxanthene- 8,3'-啕哚]-2·(1Ή)-ketone, and using l(bromomethyl)_2(trifluoromethoxy)benzene to form 0 for 1_bromopentane, to obtain Γ_[(2 -trimethoxy-aryl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4] benzodioxanthene _8,3'_吲哚] _2,(1Ή) ketone (42%) as a colorless solid: 1H NMR (300 MHz, DMSad6) 6 7 51·7 33 (m, 4 Η), 7 21 7 29 (m, 1H), 7.19 (d, J = 7.1 Hz, 1H), 7.02-7.06 (m, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.52 (s, 1H), 6.21 (s, 1H), 5.00 (ABq, 2H), 4.75 (ABq, 2H), 4.22-4.07 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 176.7, 154.7, 146.4, 144.2, 142.1, 137.8, 131.7, 129.6, 129.1, 128.8, 128.3, 127.8, 123.7, 123.2, 121.1, 120.9, 120.2, (q, JC.F= 253.9 Hz), 111.3, 109.0, 98.8, 79.5, 64.2, 63.6, 57.2 ; MS 〇(ES+)m/z 469.8 (M+l) 〇 Example 7.28 1·-[2-(2,2,5-Third -1,3-dioxolybdenum-2-yl)ethyl]_2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8, 3ι_哚哚]_2, (i,h)-ketone synthesis

According to the procedure as described in Example 7.3, and with irrelevant changes, 143924-sp-20091127-4 -601- 201020257 uses 2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene-8,3'-W哚]-2Χ1Ή)-ketone replacement (S)-2,3-dihydrospiro[,,[2,3-g][l,4 Benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one, and 2-(2-bromoethyl)-2,5,5-trimethyl-1 , 3-dioxembrane replaced 1-bromopentane to obtain Γ-[2-(2,2,5-tridecyl-1,3-dioxolan-2-yl)ethyl]-2 ,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3,-啕哚]-2·(ΓΗ)-one (23%), Colorless solid: 1 η NMR (300 MHz, CDC13) δ 7.33-7.38 (m, 1 Η), 7.15 (d, J = 7.7 Hz, 1H), 7.04 (t, J = 6.9 Hz, 2H), 6.50 (s , 1H), 6.14 (s, 1H), 4.67 (ABq, 2H), 4.22-4.05 (m, 4H), 3.96-3.71 (m, 2H), 3.49 (ABq, 4H), 2.09-1.84 (m, 2H ), 1.41 (s, 3H), 1.00 (s, 3H), 0.82 (s, 3H) ; ® 13C NMR (75 MHz, CDC13) δ 176.2, 154.6, 144.1, 142.3, 137.8, 132.0, 128.9, 123.6, 122.7 , 121.3, 111.2, 108.7, 98.7, 97.5, 79.3, 69.4, 64.2, 63.6, 57.1, 35.6, 34.9, 29.5, 2 2.6, 21.9, 19.7 &gt; MS (ES+) m/z 451.7 (M + 1). Example 8 1'-[(23)-1,4-Dioxaindole-2-ylindenyl] snail [吱,[2,3_f][i,3]benzodioxanthene _7, Synthesis of 3'-p? Budu]-2'(1Ή)-ketone

Snail [bito[2,3-f][l,3]benzodioxolene-7,3,_w哚]_2, (ΓΗ)-ketone (0.30 g '1.07 mmol) and The mixture of ruthenium sulphate (0.56 g, 1.71 mmol) in ν, Ν-dimethyl decylamine (7 mL) was stirred at ambient temperature under nitrogen for 40 min. In this mixture, 'addition of potassium hydride (〇〇5g, 〇28mmol) and (R)-(l,4-dioxoindolin-2-yl)methyl 4-(n-phenylbenzenesulfonate) 〇·38 grams, 1.4 〇 millimoles). The reaction was allowed to warm to 6 CTC&apos; and stirred for 2 h. The solvent was removed under reduced pressure, and the residue was suspended in ethyl acetate and filtered over EtOAc. The filtrate was concentrated under reduced pressure and the product was purified by flash column chromatography eluting with di-methane/tri-butyl-f-ether (19:1) to give l'-[(2S)-l, 4-dioxaindole-2-ylmethyl]spiro[furo[2,3-f][l,3]benzodioxolene-7,3,_β 哚]-2·(ΓΗ) a ketone (0.38 g, 93%) as a colorless solid: 149-149 ° C (ethyl acetate /hexane); iH NMR (300 MHz, CDC13) (diastereomers) δ 7.34-7.28 (m, 1H), 7.17 (d, J = 7.2 Hz, 1H), 7.09-7.02 (m, 2H), 6.51 (s, 1H), 6.16, 6.12 (s, 1H), 5.89-5.86 (m, 2H ), 4.81, 4.80 (2ABq, 2H), 3.99-3.55 (m, ® 8H), 3.46-3.38 (m, 1H); 13C NMR (75 MHz, CDC13) (diastereomer) δ 178.0, 177.9 , 156.0, 155.9, 149.01, 148.98, 142.7, 142.6, 142.5, 142.4, 132.3, 132.2, 129.02, 128.97, 123.94, 123.87, 123.6, 119.7, 119.5, 109.6, 109.4, 103.14, 103.07, 101.64, 101.62, 93.74, 93.72 , 80.5, 80.4, 733, 73.2, 69.4, 69.2, 66.8, 66.7, 66.53, 66.49, 58.3, 58.2, 41.9, 41.7; MS (ES+) m/z 381.9 (M + 1). Example 8.1

7'-Gas-r-[(2R)-W-hydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[丨丨:5,4-b']difuranium]-2 '(ΓΗ)-ketone synthesis

According to the procedure as described in Example 8, and the insignificant change was made using 7'-chloro-5,6-dihydrospiro[benzo[a7:5,4,7,]difuran-3,3, _吲哚]_ 2·(1Ή)_嗣Replacement snail [吱,[2,3-f][l,3]benzodioxene _7,3,_吲哚]-2 (1H )-嗣' and using this methylbenzenesulfonic acid (foot)_(tetrahydrofuran-2-yl)methyl ester substitution 143924-SD-20091127-4 201020257 4-mercaptobenzenesulfonic acid (R)-(l,4-di Oxygen-2-yl)methyl ester to give 7'-chloro-indenyl-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b : 5,4-b']difuran-3,3'-port 5丨嗓]-2'(1Ή)-one (98%), colorless solid: melting point 192-193 ° C (hexane / acetic acid Ester); NMR (300 MHz, DMSO-d6) &lt;5 7.23-7.18 (m, 1H), 7.08-6.98 (m, 2H), 6.53 (d, J = 17.6 Hz, 1H), 6.42 (d, J = 2.0 Hz, 1H), 4.80-4.69 (m, 2H), 4.53-4.47 (m, 2H), 4.20-4.11 (m, 1H), 3.95-3.60 (m, 4H), 2.99-2.93 (m, 2H ), 2.04-1.59 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 177.7, 177.6, 161.1 (2C), 160.5, 160.3, 138.3, 138.0, 135.8, 135.4, 130.7, 130.6, 124.1, 122.7 , 122.6, 120.5, 120.2, 119.9, 119.8, 119.2, 118.8, 114.3, 114.2, 92.4, 92.2, 80.0, 76.3, 76.1, 72.0, 72.0, 67.2, 66.9, 56.7, 56.5, 45.0, 44.9, 28.3, 28.2, 24.9, 24.9; MS (ES+) m/ z 397.7 (M + 1), 399.7 (M + 1). Example 8.2 7L Fluoro-r-[(2R)-tetrahydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[i,2-b:5,4-b]difuran- Synthesis of 3,3'-吲哚]-2·(1Ή)-ketone

According to the procedure as described in Example 8, and performing an insignificant change, 7'-fluoro-5,6-dihydrospiro[7:5,4_b,]difuran_3,κ哚]_ 2'(1Ή)-net replacement snail [唉 并[2,3 ship 3] benzodioxene _7,3, ten]_ 2 (1 Η)-ketone, and use 4- Methylbenzenesulfonate (R)_(tetrahydrofuran-2-yl)methyl ester was substituted for methyl 4-mercaptosuccinic acid (RM1,4-dioxolan-2-yl) methyl ester to obtain 7,-fluoro--- O-)-tetrahydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[cafe:corrective]difuran-3,3'-received]-2'--ketone (28% ) 'is a colorless solid: melting point 16917〇. (: (B 143924-sp-20091127-4 • 604-201020257 ether); 1H NMR (300 MHz, DMSO-d6) (5 7.35-7.32 (m, 1H), 7.15-7.01 (m, 2H), 6.56 ( d, J = 28.1 Hz, 1H), 6.41 (d, J = 2.9 Hz, 1H), 4.78-4.67 (m, 2H), 4.52-4.46 (m, 2H), 4.30-3.93 (m, 3H), 3.82 -3.93 (m, 2H), 2.99-2.91 (m, 2H), 2.06-1.58 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) δ 176.7, 156.8, 156.7, 154.3, 142.9, 142.7, 136.1, 136.0, 132.8, 131.5, 131.3, 128.7 (2C), 123.3 (2C), 122.7, 121.9, 121.8, 109.7, 109.6, 109.5, 104.5, 104.4, 92.4, 79.5, 75.6, 75.4, 67.1, 67.0, 57.2, 43.8, 43.7, 28.5, 28, 4, 28.1, 25.0, 24.9. Example 8.3 Fluoro-7-methyl-l'-[(2R)-rahydrofuran-2-ylindenyl]-5,6-di Synthesis of hydrogen snail [benzo[l,2-b : 5,4-b']difuran-3,3,-吲哚]-2, (1Ή> ketone

According to the procedure as described in Example 8, and performing irrelevant changes, 4'-fluoro-7-mercapto-5,6-dihydrospiro[benzo[i,2-b:5,4- b,]difuran-3,3,-吲哚]-2'(ΓΗ)-one substituted snail [吱,[2,3-f][l,3]benzodioxene-7, 3, _ ® 吲哚]-2·(1Ή)-ketone, and replacing 4-methylbenzenesulfonic acid (R) with 4-methylbenzenesulfonic acid (r)_(tetrahydrofuran-2-yl)methyl ester (l,4-diindole-2-yl) decyl ester, obtaining 4,-fluoro-7--fluorenyl-l'-[(2R)-ra-hydron-but-2-ylmethyl]- 5,6-dihydrospiro[benzo[i,2-b:5,47']dipyran-3,3'-noise]-2·(1Ή)-ketone (76%), colorless Solid: melting point 175-176 ° C (diethyl ether); 4 NMR (300 MHz, CD3OD) δ 7.14-7.06 (m, Ιίί), 6.71-6.52 (m, 2H), 6.25 (d, J = 2.3 Hz, 1H ), 4.80-4.78 (m, 2H), 4.51 (t, J = 8.6 Hz, 2H), 4.26-3.69 (m, 5H), 3.00 (t, J = 8.6 Hz, 2H), 2.56 (s, 3H) , 2.16-1.87 (m, 3H), 1.78-1.69 (m, 1H); MS (ES+) m/z 396.0 (M + 1). 143924-sp-20091127-4 -605- 201020257 Example 8.4 Γ-pentyl-2'3-dihydrospiro[吱,[2,3_幻[14]benzodioxolene-8,3 嗓]-2,(1,Η)-ketone synthesis

According to the procedure as described in Example 8, and irrelevant changes were made, 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8 was used. ,3,_吲哚]-_ 2'(1Ή)-嗣substituted snail [吱,[2,3-f][l,3]benzodioxanthene_7,3W丨哚]-2 · (1Ή)-ketone, and replacing 4-(4-diphenylindole-2-yl)methyl 4-methylbenzenesulfonate with 1-bromopentane to obtain Γ-pentyl-2,3 -Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-峋哚]-2,(1,H)-one (91%) , as colorless solid: mp 129-130 ° C (diethyl ether / hexane); 1H NMR (300 MHz, CDC13) (5 7.29 (ddd, J = 8.0, 7.7, 1.5 Hz, 1H), 7.16 (d, J = 7.5 Hz, 1H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.21 (s, 1H), 4.88 (d, J = 9.0 Hz, 1H), 4.63 (d, J = 9.0 Hz, 1H), 4.23-4.17 (m, 2H), 4.14-4.09 (m, 2H), 3.87-3.77 (m, ® 1H), 3.72- 3.62 (m, 1H), 1.77-1.68 (m, 2H), 1.45-1.30 (m, 4H), 0.91 (t, J = 6.6 Hz, 3H); 13 C NMR (75 MHz, CDC13) δ ΠΊ3, 155.3 , 144.6, 142.5, 138.3, 132.7, 128.9, 124.0, 123.2, 121.3, 111.6, 108.7, 99.4 , 80.2, 64.6, 64.0, 58.1, 40.4, 29.1, 27.2, 22.4, 14.1; MS (ES+) m/z 366.0 (M + 1). Example 8.5 (8R)-1'-[(2R)-1,4 -dioxolyl-2-ylmethyl]-2,3-dihydrospiro [bito-and-[2,3-g] [1,4]benzodioxanthene-8,3M丨哚] -2'(1Ή)-ketone synthesis•606- 143924-sp-20091127-4 (8) 201020257

Using (R)-2,3-dihydrospiro[Pfurano[2 3_g][1,4]benzodioxanthene according to the procedure as described in Example 8 and performing irrelevant changes _8,3, 嗓 嗓]-2'(1Ή)-ketone-substituted snail [吱 并 and οπυ] benzodioxolene _7,3, 嗓 嗓]-2'(1Ή)-嗣' and use (5)_2_(Mothyl fluorenyl)_14_dioxanthine (Kim, Η γ ❹ et al., 仞(10) 忒C/im. L (2005), 15: 3207-11) Replacement of 4-methylbenzene Acid (R)-(l,4-dioxoindole-2-yl) decyl ester, obtained (serving saponin)-; dioxosin-2-ylmethyl]-2,3-dihydrogen Snail [2,3-g][l,4]benzodioxanthene-8,3,-啕哚]-2|(1Ή)-one (51%) as a colorless solid: Melting point 198-199. (: (ether/hexane); 1H NMR (300 MHz, CDC13) accounted for 7.30 (ddd, J = 7.8, 7.8, U Hz, 1H), 7.16 (d, J = 7.8 Hz, 1H), 7.08-7.02 ( m, 2H), 6.49 (s, 1H), 6.24 (s, 1H), 4.88 (d, J = 9.0 Hz, 1H), 4.64 (d, J = 9.0 Hz, 1H), 4.22-4.16 (m, 2H) ), 4.13-4.08 (m, 2H), 3.98-3.78 (m, 4H), 3.75-3.56 (m, 4H), 3.47-3.38 (m, 1H); 13 C NMR (75 φ MHz, CDC13) 5 177.9 , 155.3, 144.7, 142.7, 138.4, 132.4, 128.9, 123.8, 123.5, 121.3, 111.7, 109.6, 99.5, 80.1, 73.3, 69.2, 66.7, 66.5, 64.6, 64.0, 58.1, 41.8 ; MS (ES+) m/z 396.0 (M + 1) » Example 8.6 (8R)-r-[(2S)-l,4-Dioxylyl-2-ylindenyl]-2,3-dihydrospiro[吱,[2, 3-g] Synthesis of [1,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one 143924-sp.20091127-4 -607- 201020257

According to the procedure as described in Example 8 and using irrelevant changes, (R)-2,3-dihydrospiro[?,2,3_g][i,4]benzoindole _8,3,_p bow 丨哚]-2·(1Ή)-ketone-substituted snail [吱吱和阳-幻(10)] benzodioxene _7 3,_P丨哚丨哚]-2'(1Ή a ketone to obtain dioxostigmine-2-ylmethyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8, 3'-吲哚]-2,(1Ή)-one (88%), as a colorless solid: m.p. 207-209°C (diethyl ether/hexane); NMRGOOMHz, CDC13) ά 7.30 (ddd, J = 7.7, 7.7, 1.3 Hz, 1H), 7.15 (dd, J = 7.5, 0.9 Hz, 1H), 7.08-7.02 (m, 2H), 6.49 (s, 1H), 6.21 (s, 1H), 4.87 (d, J = 9.0 Hz, 1H), 4.63 (d, J = 9.0 Hz, 1H), 4.21-4.16 (m, 2H), 4.13-4.08 (m, 2H), 3.98-3.79 (m, 4H), 3.75-3.56 ( m, 4H), 3.41 (dd, J = 11.6, 9.8 Hz, 1H); 13C NMR (75 MHz, CDCI3) &lt;5 177.8, 155.3, 144.7, 142.7, 138.4, 132.3, 128.9, 123.9, 123.5, 121.1, 111.6, 109.4, 99.5, 80.2, 73.3, 69.4, 66.8, 66.5, 64.6, 64.0, 58.0, 41.9; MS (ES+) m/z 396.0 (M + 1). Example 8.7 (8S)-1'-[(2SH,4-Dioxaindole-2-ylmethyl)_2,3-dihydrospiro[吱,[2,3-g][l,4]benzene Synthesis of dioxin terpene _83, _, 哚]_2, (ΓΗ) ketone

According to the procedure as described in Example 8, and irrelevant changes were performed, 143924-sp-20091127-4 -608- 201020257 using (S)-2,3-dihydrospiro[furo[2,3-g] [l,4]benzodioxanthene-8,3L吲哚]-ΑΓΗ)-ketone-substituted snail [吱,[2,3-ί][1,3]benzodioxanthene- 7,3··-?丨哚]-2·(1Ή)-ketone, (8S)-1'-[(2S)-1,4-dioxoindolin-2-ylmethyl]-2, 3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-2'(1Ή)-one (92%), Colorless solid: mp 198-200 ° C (diethyl ether / hexanes); 1H NMR (300 ΜΗζ, CDC13) (5 7.30 (ddd, J = 7.8, 7.5, 1.2 Hz, 1H), 7.15 (dd, J = 7.5 , 1.2 Hz, 1H), 7.08-7.01 (m, 2H), 6.49 (s, 1H), 6.24 (s, 1H), 4.88 (d, J = 9.0 Hz, 1H), 4.64 (d, J = 9.0 Hz , 1H), 4.21-4.16 (m, 2H), 4.14-4.09 (m, 2H), 3.98- 3.79 (m, 4H), s. 3.74-3.55 (m, 4H), 3.42 (dd, J = 11.6, 9.5 Hz, 1H) ; 13C NMR (75 MHz, CDC13) δ 177.9, 155.2, 144.7, 142.7, 138.4, 132.4, 128.9, 123.8, 123.5, 121.3, 111.7, 109.6, 99.5, 80.0, 73.3, 69.2, 66.7, 66.5, 64.6, 64.0, 58.1, 41.8 ; MS (ES+) m/z 396.0 (M + 1). Example 8.8 (8S)-1'-[(2R)-1,4-Dioxin-2-ylindenyl]_2,3-dihydrospiro[吱,[2, Synthesis of 3-g][l,4]benzodioxanthene -8,3·-沔卜朵]_2'(ιή)-ketone

According to the procedure as described in Example 8, and with irrelevant changes, use (S)-2'3-dihydrospiro[furo[2,3-g][l,4] stupid and dioxane Alkene _8,3·_ρ?丨哚]-2'(1Ή)-ketone substituted snail [furobenzo benzodioxene _7,3, Qiao 哚]-2 (1 H)-ketone, and used 4-methylbenzenesulfonic acid (8)_(1,4-dioxaindole-2-yl)methionin-substituted 4-methylphenyl acid (r)_(i,4-dioxanthene-2-yl)methyl ester , (8S)_1L 143924-sp-20091127-4 •609- 201020257 [(2R)-1,4-Dioxaindole-2-ylindenyl]-2,3-dihydrospiro[Embed [ 2,3-g][l,4]benzodioxanthene-8,3·-啕哚]-2'(1Ή)-one (84%), colorless solid: mp 207-210 ° C (diethyl ether / hexane); 1H NMR (300 MHz, CDC13) (5 7.30 (ddd, J = 7.7, 7.7, 1.2 Hz, 1H), 7.15 (dd, J = 7.5 Hz, 0.9 Hz, 1H), 7.08- 7.02 (m, 2H), 6.49 (s, 1H), 6.21 (s, 1H), 4.87 (d, J = 9.0 Hz, 1H), 4.63 (d, J = 9.0 Hz, 1H), 4.21-4.16 (m , 2H), 4.13-4.09 (m, 2H), 3.98-3.77 (m, 4H), 3.75-3.56 (m, 4H), 3.41 (dd, J =11.7, 9.9 Hz, 1H) ; 13C NMR (75 MHz , CDC13) δ 177.8, 155.3, 144.7, 142.7, 138.4, 132.3, 128.9, 123.9, 123.5, 121.1, 111.6, 109.4, 99.5, 80.2, 73.3, 69.4, 66.8, 66.5, 64.6, 64.0, 58.0, 41.9; MS (ES+) m/z 396.0 (M + 1). Example 8.9 r-[( Synthesis of 2R)-tetrahydrofuran-2-ylindenyl]_6,7-dihydrospiro[benzo[u-7:4,5_b,]difuran-3,3'-啕哚]々'(ΓΗ)-one

According to the procedure as described in Example 8, and the insignificant change was made, using 6,7-dihydrospiro[benzo[i,2:7:5,7,7]difuran_33,_啕哚]_2 , (1Ή) ketone-substituted snail [吱,[2,3-f][l,3]benzodioxolene-7,3,·,哚]-2'(1Ή)-net, and used (R)-(tetrahydrofuran-2-yl) decyl ester of 4-methylbenzenesulfonic acid was substituted for (R)-(l,4-dioxaindole-2-yl)methyl 4-methylbenzenesulfonate to obtain r_[ (2R)_tetrahydrofuran-2-ylmethyl]-6,7-dihydrospiro[stupid and like seven:4,5_b]difuran_3,3,_啕哚]_2, (1Ή) ketone (57% ), as a colorless solid: mp 162-164. (: (diethyl ether / hexane); 1H NMR (300 MHz 'CDCI3) (diastereomer) occupies 7 29 qing] = 7 8, 7 8 Hz, m), 7 16_ 7.00 (m, 3H), 6.79 (s, 1H), 6.12 (s, 1H), 4.91 (d, J = 9.0 Hz, 1H), 4.65 (d, J = 143924-sp-20091127-4 -610- 201020257 9.0 Hz, 1H), 4.48 (t, J = 8.7 Hz, 2H), 4.31-4.22 (m, 1H), 4.00-3.67 (m, 4H), 3.14 (t, J = 8.7 Hz, 2H), 2.09-1.82 (m, 3H), 1.78-1.67 (m, 1H) ; 13 C NMR (75 MHz, CDCI3) ( diastereomers) s 178 〇, 177 8, 155丄154 9, 143丄142.9, 132.3, 132.2, 128.94, 128.88, 128.7, 127.91, 127.86, 123.8, 123.7, 123.4, 109.9, 109.5, 107.1, 104.01, 103.96, 80.2, 80.1, 77.1, 76.8, 71.7, 68.4, 68.3, 58.52, 58.49, 44.7, 30.4, 29.4, 29.0, 25.9, 25.7; MS (ES+) m/z 364.0 (M + 1). Example 8.10 ® ???)-1,4-Dioxindole-2-ylindenyl]-6,7-dihydrospiro[benzo[l,2-b:4,5-b,]difuran- Synthesis of 3,3'-吲哚]-2'(1Ή)-ketone

According to the procedure as described in Example 8, and performing irrelevant changes, 6,7-dihydrospiro[benzo-like 7:4,5-b]difuran-3,34哚]_2,(1Ή)one was used.换 Change the snail [吱11南和[2Χ[1,3]benzodioxol-7,3,- 哚哚]-ΑΓΗ)-ketone, and use 4-methylbenzenesulfonic acid (8)_(1, 4_Dioxetan_2_yl)methyl ester replaces 4-methylbenzene acid (8)_(1,4-dioxaindole-2-yl) decyl ester to obtain 1,-[(2R)-1,4 - Dioxostigmine-2-ylmethyl]-6,7-dihydrospiro [benzo-like 7:4,5-b,]difuran-3,3·-啕哚]-2, (1Ή) - 酉同(97%) ' is a colorless solid: melting point 162_164. 〇 (diethyl ether / hexane); Li (300 MHz, CDC13) (diastereomer) accounted for 7.302, 7.298 (ddd, J = 7.8, 7.7, 1.3 Hz, 1H), 7.17-7.14 (m, 1H) ), 7.07-7.02 (m, 2H), 6.79 (s, 1H), 6.12, 6.09 (s, 1H), 4.91, 4.90 (d, J = 8.9 Hz, 1H), 4.66, 4.65 (d, J = 8.9 Hz, 1H), 4.48 (t, J = 8.7 Hz, 2H), 3.98-3.78 (m, 4H), 3.75-3.55 (m, 4H), 3.45-3.37 (m, 1H), 3.14 (t, 143924- Sp-20091127-4 -611- 201020257 J = 8.7 Hz, 2H); 13 C NMR (75 MHz, CDC13) (diastereomers) (5 177.9, 177.7, 155.1, 155.0, 154.92, 154.88, 142.8, 142.7, 132.3, 132.2, 128.94, 128.89, 128.84, 128.80, 127.8, 127.7, 123.9, 123.8, 123.5, 109.6, 109.4, 107.19, 107.16, 104.0, 103.9, 80.0, 79.9, 73.3, 71,7, 69.4, 69.2, 66·8, 66.7, 66.52, 66.48, 58.46, 58.43, 41.9, 41.8, 30.4; MS (ES+) m/z 380.0 (Μ + 1). Example 8.11 l'-[(2R)-ra Hydrofuran-2-曱 ]]-3,4-dihydro-2-indole-spiro[吱,[2,3-h][l,5]benzoxaoxy-7 ]-2'(1Ή)-嗣 Synthesis

Using 3,4-dihydro-2Η-spiroindole and [2,3-h][l,5]benzodiazepines octadecene_9,3'_啕哚]-2'(1Ή) -ketone-substituted snail [吱,[2,3-f][l,3] benzodioxanthene-7,3,_啕哚]-2'(1Ή)-one, and 4-a Substituting (8)-(pentahydrofuran-2-yl) decyl benzenesulfonate for the replacement of 4-mercaptophenyl acid (R)-(l,4-dioxoindolin-2-yl)methyl ester to obtain i, _[ (2R)_tetrahydrofuran-2-ylmethyl]-3,4-dihydro-2H-spiro [bito-and-[2,3-h][l,5]benzodioxanthene] -2'(1Ή)-ketone (80%) 'as colorless solid: melting point 134-138C (diethyl ether / hexanes); 4 NMR (300 MHz, CDC13) (diastereomers) δ 7.29 ( Dd, J = 7.8, 7.8 Hz, 1H), 7.14-7.01 (m, 3H), 6.58 (s, 1H), 6.36 (s, 1H), 4.91 (d, J = 9.0 Hz, 1H), 4.66 (d , J = 9.0 Hz, 1H), 4.31-4, 18 (m, 2H), 4.12-4.04 (m, 2H), 4.01-3.68 (m, 5H), 2.21-1.85 (m, 5H), 1.77-1.66 (m, 1H) ' 13 C NMR (75 MHz, CDC 13) (diastereomer) 6 i78. 〇, 177.8, 156·8, 153.0, 146.3, 143·0, 142.9, 132.3, 132.2, 128.94, 128 90 123 9 123 8 143924-sp-20091127-4 -612- 201020257 123.4, 123.34, 123.28, 116.14, 11 6.10, 109.8, 109.6, 103.5, 80.58, 77.1, 76.9, 70.9, 68.4, 68,3, 58.04, 58.02, 44.7, 32.3, 29.4, 29.1,25.9, 25.7 ; MS (ES+) m/z 394.1 (Μ + 1 ). Example 8.12 r-[(2R)-l,4-Dioxaindole-2-ylindenyl]-3,4-dihydro-2Η-spiro[吱,[2,3-7][1,5] Synthesis of benzodiazepine heptarene-9,3'-吲哚]-2'(1'11)-one

According to the procedure as described in Example 8, and irrelevant changes were made, using 3,4-dihydro-2Η-spiro[吱,[2,3-h][l,5]benzodioxan-7 Terpene-9,3'-吲哚]-2'(1Ή)-ketone-substituted snail [吱,[2,3-f][l,3]benzodioxene-7,3·-啕哚]-2Χ1Ή)-阙, and (5)-2-(Ethyl decyl)-1,4-dioxane hydrazine is used to replace 4-methylbenzenesulfonic acid (R)-(l,4-dioxene) -2--2-yl) oxime ester, obtaining l'-[(2R)-l,4-dioxoin-2-ylmethyl]-3,4-diar-argon-2H-spiro[吱喃[2 , 3-h][l,5]benzodioxan φ heptaene-93'-啕哚]-2·(ΓΗ)-one (61%), as colorless solid: mp 144-147. (: (diethyl ether / hexane); WNMR (300 MHz, CDC13) (diastereomer) as 7.30 (ddd, J = 7.7, 7.7, 1.0 Hz, 1H), 7.14 (d, J = 6.9 Hz, 1H), 7.08-7.02 (m, 2H), 6.59 (s, 1H), 6.36, 6.33 (s, 1H), 4.91, 4.90 (d, J = 9.0 Hz, 1H), 4.67, 4.66 (d, J = 9.0 Hz, 1H), 4.28-4.19 (m, 1H), 4.15-4.02 (m, 2H), 3.99-3.78 (m, 5H), 3.75-3.57 (m, 4H), 3.46-3.39 (m, 1H) , 2.22-2.00 (m, 2H); 13C NMR (75 MHz, CDC13) (diastereomers) 5 177.8, 177.7, 156.8, 156.7, 153.1, 153.0, 146.4, 146,3, 142.65, 142.63, 132.3 , 132.2, 129.0, 128.9, 124.0, 123.9, 143924-sp-20091127-4 -613- 201020257 123.6, 123.2, 123.1, 116.1, 116.0, 109.6, 109.4, 103.58, 103.56, 80.5, 80.4, 73.34, 73.30, 70.9, 69.4, 69.2, 66.8, 66.7, 66.52, 66.49, 57'98, 57.96, 41.9, 41.8, 32.3; MS (ES+) m/z 410.0 (Μ + 1). Example 8.13 1 -[(2S)-1,4 -monooxan-2-ylindenyl]-3,4-dihydro-2H-spiro[, succinyl[2,3-h][l,5]benzodioxane I squaring _9, 3, _ Ling Duoqing - the synthesis of ketone

According to the procedure as described in Example 8, and irrelevant changes were made, using 3,4-dihydro-2H-spirobofo[2,3-h][l,5]benzodioxine-7 Alkenin-9,3,-峋哚]-2'(1Ή)-ketone-substituted snail [Bisto[2,3-f][l,3]benzodioxol-7,3,- (9) 哚]-2·(1Ή)-ketone' and replacing 4-mercaptobenzenesulfonic acid with (S)-(l,4-dioxoin-2-yl)methyl ester of 4-methylbenzenesulfonic acid ( R) _(i,4-dioxoindole-2-yl)methyl ester to obtain r-[(2S)-l,4-dioxolyl-2-ylmethyl]-3,4-dihydro -2H-spiro[吱,[2,3-h][1,5]benzodioxine-7-ocylene-9,3'-啕哚]-2·(1Ή)-one (91%), Colorless solid: mp 137-139 ° C (hexanes /EtOAc); 1H NMR (300 MHz, CDC13) (diastereomers) (5 7.33-7.27 (m, 1H), 7.14 (d, J = 7.2 Hz, 1H), 7.08-7.01 (m, 2H), 6.58 (s, 1H), 6.36, 6.33 (s, 1H), 4.91, 4.90 (d, J = 9.0 Hz, 1H), 4.67, 4.66 (d , J = 9.0 Hz, 1H), 4.28-4.20 (m, 1H), 4.14-4.02 (m, 2H), 3.99-3.78 (m, 5H), 3.76-3.57 (m, 4H), 3.46-3.38 (m , 1H), 2.22-2.00 (m, 2H); 13C NMR (75 MHz, CDC13) ( diastereomers) 5 177.8, 177.7, 156.8, 156.7, 153.08, 153.05, 146.38, 146.35, 142.65, 142.63, 132.3, 132.2, 129.0, 128.9, 124.0, 123.9, 123.6, 123.2, 123.1, 116.1, 116.0, 109.6, 109.4, 103.59, 103.56, 80.5, 143924-SO- 20091127-4 -614- 201020257 80.4' 73·34, 73.31, 70.9, 69.4, 69.2, 66.8, 66.7, 66.52, 66.49, 57.98, 57.96, 41.9, 41.8, 32.3; MS(ES+)m/z410O(M+l Example 8.14 3-mercapto-r-(((R)'hydrofuran-2-yl)methyl)_2H spiro[benzofuro[6,5 d]^嗤-7,3'-dihydrogen Synthesis of 哚[], 2,2|(3H,6H)-dione

According to the procedure as described in Example 8 and the insignificant changes were made, 3-mercapto-snail [bito-and-[2,3-f][l,3]benzo, oxazole-7,3'-吲哚]-2,2'(1Ή,3Η)-dione-substituted snail [吱,[2,3-f][l,3]benzodioxanthene_7,3'_啕哚] -2'(1Ή)-ketone' and replace 4-(methyl)sulfonic acid (R)-(tetrahydrofuran-2-yl)methyl ester with 4-methylbenzenesulfonic acid (R)-(l,4-dioxo圜 圜-2-yl)methyl ester to give 3-methyl-1,-(((R)-tetrahydrofuran-2-yl)methyl)-2H-spiro[benzofuro[6,5-d] Carbazole-7,3'-dihydroanthracene-2,2'(311,611)-dione (69%), as colorless solid: mp 186-187. (:(Ethyl ether); 1H NMR (300 MHz, DMSO-d6) δ 7.36-7.29 (m, 1H), 7.23 (d, J = 8.2)

Hz, 1H), 7.14 (d, J = 8.2 Hz, 1H), 7.06-7.02 (m, 2H), 6.63 (d, J = 6.9 Hz, 1H), 4.85-4.73 (m, 2H), 4.24-4.16 (m, 1H), 3.81-3.59 (m, 4H), 3.31 (s, 3H), 2.00-1.75 (m, 3H), 1.69-1.55 (m, 1H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.2, 157.3, 154.9, 143.4, 136.6, 133.3, 131.9, 129.3, 123.9, 123.3, 122.3, 110.2, 105.0, 92.9, 80.0, 76.1, 67.7, 57.7, 44.3, 29.1, 28.6, 25.5 ; MS (ES+) m /z 392.7 (M + 1). Example 8.15 7'-Fluoro-indenyl-(pyridin-2-ylmethyl)-3,7-dihydro-2H-spiro [benzofuran 143924-sp-20091127-4 -615- 201020257 [5'6 -b][l,4]dioxanthene·8,3,dihydroanthracene]_2, synthesis of ruthenium

According to the procedure as described in Example 8, and the insignificant change was made, 7·-fluoro-2,3-dihydrospiro[2 3_g][1,4]benzodioxanthene was used. Alkene_8,3,_W嗓]-2'(1Ή)-_substituted snail [唉喃和阳耶(3) benzodioxolane _7,3,_ Η卜来]-2'(1Ή) - Copper' and using 4-(bromomethyl)pyridinium hydrobromide to replace (R)-(l,4-dioxoland-2-yl)methyl ketone 4-methylbenzenesulfonate 7,-fluoro-indolylpyridin-2-ylmethyl)-3,7-dihydro-2H-spiro[benzofuro[5,6-b][l,4]dioxene terpene -8,3,-diazepine]-2'-bright (38%), colorless solid: mp 205-207 ° C (di- methane); 1H NMR (300 MHz, CDC13) δ 8.55 (d , J = 4.8 Hz, 1H), 7.69-7.63 (m, 1H), 7.23-7.16 (m, 2H), 6.99-6.89 (m, 3H), 6.50 (s, 2H), 5.35 (d, J = 16.4 Hz, 1H), 5.17 (d, J = 16.4 Hz, 1H), 4.97 (d, J = 8.9 Hz, 1H), 4.70 (d, J = 8.9 Hz, 1H), 4.22-4.19 (m, 2H), 4.15-4.13 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 177.5, 155.7, 155.1, 149.6, 144.7, 138.4, 136.7, 124.0, 124.0, 122.4, 121.0, 120.7, 119.7, 119.6, 116.7, 116.5 , 112.1, 99.3, 80.3, 64. 5, 63.9, 58.4, 47.0; MS (ES+) m/z 405.0 (M + 1). Example 8.16 7匕Fluoro-fluorenyl-((3-(trifluoromethyl)pyridin-2-yl)methyl)-3,7-dihydro-2H-spiro[benzofuran[5,6-7] Synthesis of [1,4]dioxanthene-8,3'-dihydroanthracene-2'-one 143924-SO-20091127-4 • 616- 201020257

According to the procedure as described in Example 8, and inconsequential changes were made, using 7'-fluoro-2,3-dihydrospiro[c-buto[2,3_g][1,4]benzodioxan Terpene oxime]-2'(ΓΗ)-ketone-substituted suffolop-benzo-dioxy-n-decene _7,3,_ 啕哚]-2'(1Ή)-one, and 2_(gas base Methyl)_3_(trifluoromethylcyclopyridine hydrochloride φ salt replaces 4-methylbenzenesulfonic acid (RMM-dioxan-2-yl)methine vinegar to obtain 7,-fluoro-indole-((3- (trifluoromethylcyclopyridin-2-yl)indolyl)_3,7-dihydro-2H-spiro[benzofuro[5,6-b][l,4]dioxopinene-8, 3'-Dihydroanthracene]_2, 嗣 (40%), as a colorless solid: mp 241-243 ° C (di- methane); 1 η NMR (300 MHz, CDC13) occupies 8.62 (d, J = 4.7) Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.34-7.30 (m, 1H), 7.00-6.86 (m, 3H), 6.68 (s, 1H), 6.50 (s, 1H), 5.54 (d, J = 17.1 Hz, 1H), 5.37 (d, J = 17.1 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.73 (d, J = 9.0 Hz, 1H), 4.21-4.19 (m, 2H), 4.15-4.14 (m, 2H); 13C NMR (75 MHz, CDC13) δ 177.9, 155.1, 153.0, 〇151.9, 149.2, 145.9, 144.7, 138.3, 135.5, 134.3, 129.2, 123.9, 121.9 , 12 1.3, 119.6, 116.4, 116.2, 112.5, 99.2, 80.2, 64.6, 63.9, 58.5, 44.2; MS (ES+) m/z 473.0 (M + 1). Example 8.17 3'-[2-(Difluoroindenyl)爷基]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,1'-茚]-2·(3Ή)-one Synthesis 143924-sp-20091127^ •617- 201020257

According to the procedure as described in Example 8, and the insignificant change was made, 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8 was used. ,3,_吲p木]-2(1 H)-ketone-substituted snail [吱-benzo-benzodioxyl]- ketone, and using l (bromo group) Methyl) 2 (difluoromethyl)benzene replaces (R)-(l,4-dioxaindole-2-yl) decyl ester of 4-methylbenzenesulfonic acid to obtain 3,_[2 (difluorodecyl)爷基]-2'3_Dihydrospiro [bite-and-[2,3-g][l,4] benzodioxanthene-8, Γ-茚]-2(3'11)- Ketone (52%) as colorless solid: mp 191.匚;]1^]^(30〇]\«^, DMSO-d6) δ 7.67 (d, J = 7.4 Hz, 1H), 7.52-7.46 (m, 2H), 7.37 (s, 1H), 7.26- 7.20 (m, 3H), 7.06 (dd, J = 7.4, 7.4 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.24 (s, 1H), 5.17-5.04 (m, 2H), 4.77 (ABq, 2H), 4.20-4.11 (m, 4H); 13CNMR (75MHz, DMSO-d6) δ 177.4, 155.3, 144.7, 142.6, 138.3, 134.5 (t, JC.F = 3.8 Hz), 132.1, 131.9, 131.8 (t, JC.F = 21.3 Hz), 129.3, 128.3, 127.4, 127.0 (t, Jc-F = 7.7 Hz), 124.3, 123.7, 121.5, 114.9 (t, JC.F = 236.0 Hz), 111.8, 109.8, 99.3, 80.1, 64.7, 64.1, 57.8; MS (ES+) m/z 435.7 (M + 1). Example 8.18 14(5-fluoropyridinyl)methyl]-2,3-dihydrospiro[N,3-g][l,4]benzodioxanthene-8,3 Synthesis of %5丨哚]-2\1Ή)-ketone 143924-SP-20091127-4 -618- 201020257

Refer to the procedure described in Example 8 and perform irrelevant changes using 2,3-dihydrospiro[吱,[2,3^1,4]benzodioxanene m 哚] -2'(1Ή)-ketone-substituted snail [吱,[2,3-f][l,3]benzodioxanthene _7,3,_p?丨哚]-2Χ1Ή)-ketone and used 3-(Alkylmethyl)-5-fluoropyridine hydrochloride (Carls〇n et al, Acto P/wmacewiica 1972, 9, 411-414) Displaces 4-mercaptobenzenesulfonic acid (R)-(l , 4-dioxolyl-2-yl) decyl ester, 1,-[(5-fluoropyridinyl)indenyl]- 2,3-dihydrospiro[, s-[2,3-g ][l,4]benzodioxanene·8,3·_吲哚]_2, (1Ή)-ketone (71%), as a colorless solid: iHNMR (300MHz, CDCl3) d 8.45-8.38 (m , 2H), 7.37-7.34 (m, 1H), 7.24-7.14 (m, 2H), 7.04-7.00 (m, 1H), 6.78-6.75 (m, 1H), 6.46 (s, 1H), 6.17 (s , 1H), 5.03-4.85 (m, 3H), 4.64-4.61 (m, 1H), 4.16-4.04 (m, 4H); 13C NMR (75 MHz, CDC13) 5 177.6, 1553, 144.7, 144.6, 141.4, 138.4, 138.1, 137.8, 132.1, 129.0, 124.3, 123.9, 122.1, 121.9, 120.6, 111.4, 108.8, 99.5, 80.1, 64.5, 63.9, 58.0, 41.1 I MS (ES+) m/z 405.0 (M + 1). Example 8.19 (8S)-r-[(5-Fluoropyridin-3-yl)indolyl]-2,3-dihydrospiro 1&gt; Furano[2,3-g][l,4]Benzene Synthesis of Dioxinol-8,3'-啕哚]-2Χ1Ή)-one

143924-sp-20091127-4 -619 201020257 (8S)-2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8 3,_u In the solution of 2-butanone (15 ml), add the carbonic acid planer (1.76 g, 5.40 mmol), 3_( Gas-based methyl)_5-fluoropyridine hydrochloride (0.49 g ' 2.69 mmol) and potassium iodide (0.085 g, 38 mol %). The mixture was stirred under nitrogen at ambient temperature for 72 hours. Further, a carbonated planer (1.76 g, 5.40 mmol), 3-(a gas-based mercapto)fluoropyridine hydrochloride (0.49 g, 2.69 mmol) and tetra-n-butylammonium iodide (added) were added. 〇〇8 g, 〇22 mmol) and the reaction mixture was heated under reflux for 48 hours, allowed to cool to ambient temperature ' filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with a gradient of 10% to 40% of ethyl acetate in hexane, and recrystallized from diethyl ether to give (8S)-l'-[(5-fluoro) Pyridin-3-yl)indenyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3·-啕哚] -2·(1Ή)-one (102.1 mg, 19%) as a yellow solid: m.p. 197-200°C (diethyl ether); 1HNMR (300 MHz, CDC13) δ 8.48-8.42 (m, 2H), 7.40-7.37 (m, 1H), 7.26-7.17 (m, 2H), 7.08-7.03 (m, 1H), 6.78-6.76 (m, 1H), 6.50 (s, 1H), 6.18 (s, 1H), 5.06-4.88 (m, 3H), 4.66-4.63 (m, 1H), 4.20-4.09 (m, 4H); 13 C NMR (75 MHz, ❹ CDC13) δ 177.7, 155.3, 144.8, 144.4, 141.3, 138.4, 138.0, 137.7 , 132.1, 129.0, 124.3, 124.0, 122.4, 122.2, 120.5, 111.4, 108.7, 99.5, 80.1, 64.5, 63.9, 58.0. 41.1; MS (ES+) m/z 404.9 (M+l). Example 9 3-methyltrifluoromethyl)furan-2-yl]methyl}spiro[吱,[3,2-f][l,2] benzisoxazole-5,3. 5丨哚Synthesis of -2'(1Ή)-ketone 143924-sp-20091127-4 -620-

201020257

3-methylspiro[, benzo benzoisoxazole _5,3, 峋哚] 2, (1 Ή) 嗣 0.2 (0.29 g ' 1.00 mmol) in Ν Ν dimethyl dimethyl hydrazine ( Sodium hydride (〇〇5 g, 1.25 mmol) was added at 〇 ° C in a stirred solution of 1 〇 ml). The reaction mixture was stirred at (TC for 3 min, then 2_(bromomethyl)_5_((dimethyl) oxime (0.25 ml ' 1.80 mmol) and the mixture was stirred at ambient temperature for 20 h. Diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, and filtered and evaporated. The filtrate was concentrated in vacuo. The residue was purified by column chromatography using ethyl acetate % to 4〇% Gradient)' to give 3-mercapto-purine-{[5-(trifluoromethyl)pyran-2-yl]methyl} snail [biting and [3,2-f] [l,2] benzoisoxazole _5,3,_吲哚]-2'(ΓΗ)-one (0.35 g, 80%): m.p. 111-112 ° C (diethyl ether / hexane); 1H NMR (300 MHz, CDC13) &lt;5 7.46 (d, J φ = 9.0 Hz, 1H), 7.33-7.27 (m, 1H), 7.15-7.12 (m, 1H), 7.06-7.01 (m, 3H), 6.77 -6.76 (m, 1H), 6.55-6.52 (m, 1H), 5.20-4.85 (m, 4H), 2.44 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 175.7, 163.9, 158.1, 154.9 , 151.6, 141.4, 130.2, 129.5, 123.9, 123.1, 120.7, 117.9, 117.1, 112.9, 109.3, 108.9, 108.8, 107.9, 81.2, 56.2, 37.5, 9.8; MS (ES+)m/z 462.9 (M +23) Example 9. 1 142-(2-methoxyethoxy)ethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran-3J-吲哚]-2 Synthesis of '(1Ή)-ketone η 143924-sp-20091127-4 -621 - 201020257

According to the procedure as described in Example 9, and the insignificant change was made, 5,6~2 snail [benzo[l,2-b:5,4-b']difuran-3,3:峋哚]-2,(1Ή)-_ replaces 3-methylspib- oxa[3,2_叩,2]benzisoxazole_5 31_啕哚]_2,(1Ή)-one, and Displacement of 2-(bromomethyl)-5-(trifluoromethyl)anthracene with 1-enyl-2-(2-methoxyethoxy)ethane to give 5,6-dihydrospiro[benzo[ l,2-b: 5,4-b,]difuran-3,3,-n-)-2'(1Ή)-one (68%), as a colorless solid: m.p. 300 MHz, CDC13) δ 7.32-7.24 (m, 1Η), 7.18-7.12 (m, 1H), 7.07-7.00 (m, 2H), 6.49 (s, 1H), 6.40 (s, 1H), 4.80 (ABq , 2H), 4.53 (t, J = 8.6 Hz, 2H), 4.09-3.88 (m, 2H), 3.83-3.73 (m, 2H), 3.68-3.60 (m, 2H), 3.53-3.46 (m, 2H ), 3.34 (s, 3H), 3.04-2.94 (m, 2H); 13 C NMR (75 MHz, CDC13) 5 177.9, 161.7, 161.2, 142.5, 132.8, 128.6, 123.7, 123.2, 120.3, 119.8, 118.9, 109.1, 93.1, 80.5, 72.3, 71·9, 70.3, 68.1, 59.0, 57.6, 40.1, 29·0; MS (ES+) m/z 382.1 (M+l). Example 9.2 r-{[(2s)-5-ketotetrahydropyrrole_2-yl]indolyl 5,6 dihydrospiro[benzo:5,4-b']difuran_3,3,_啕哚]_2ι(1Ή), the synthesis

Follow the procedure as described in Example 9, and perform an insignificant change 143924-sp-20091127-4 -622· 201020257 using 5,6-dihydrospiro[benzo[i,2-b:5,4-b ']二夫夫"南-3,3^5卜朵]-2'(1Ή)-阙 replacement of 3-methylspiro[furo[3,2-f][l,2]benzisoxazole _5,3,-吲哚]-2,(1Ή)-ketone' and replace with 2-methylbenzoic acid (S)-(5-yltetrahydroindole-2-yl)methyl ester 2- (bromomethyl)-5-(trifluoromethyl)pyran, obtaining l'-{[(2S)-5-ketotetrahydropyrrol-2-yl]indolyl}-5,6-dihydro Snail [benzo[l,2-b: 5,4-b']di-p. South _3,3'_4丨哚]-2·(1Ή)-ketone (47%), colorless solid: 133-136. H; iHNMRpOOMHz, CDC13) δ Ί35-Ί.21 (m, 1H), 7.24-7.14 (m, 1H), 7.14-7.03 (m, 1H), 7.00-6.85 (m, 1H), 6.54-6.42 (m , 1H), 6.42-6.37 (m, 1H), 4.93 (t, J = 9.3 Hz, 1H), ❿ 4.67 (dd, J = 9.3, 3.0 Hz, 1H), 4.53 (t, J = 8.5 Hz, 2H ), 4.18-4.04 (m, 1H), 3.93 (dt, J = 13.9, 4.6 Hz, 1H), 3.72 (dt, J = 13.9, 4.6 Hz, 1H), 3.07-2.80 (m, 3H), 2.42- 2.15 (m, 3H), 2.06-1.81 (m, 1H); 13 C NMR (75 MHz, CDC13) &lt;5 178.6, 178.5, 161.8 (2C), 161.3, 161.2, 142.2, 142.1, 132.6, 132.5, 129.0 (2C), 128.9, 128.8, 124.1, 123.6, 119.9 (3C), 119.7, 118.8, 108.3, 93.2, 93.1, 80.6, 80.5, 72.3, 57.5, 53.2, 53.1, 45.2 (2C), 29.6, 29.6, 28.9, 24.7 (2C) ; MS (ES+) m/z 377.1 (M + 1).

Example 9.3 Γ-[2-(2-keto-1,3-tetrahydrocarbazole)ethyl]_5,6-dihydrospiro[benzo[i,2-b: 5,4-b' Synthesis of difuran-3,3,-anthracene-2'(1Ή)-one

5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-呻 was used according to the procedure described in Example 9, and the insignificant changes were made.哚]-2,(1Ή)-ketone replacement 143924-sp-20091127-4 •623· 201020257 3-methylspiro[c-buto[3,2-f][l,2]benzisoxazole-5 , 3'-吲哚]-2'(1Ή)-ketone, and 2-(2-ketotetrahydropurine*»圭-3-yl) 4-acetate was replaced with 4-mercaptobenzoic acid 2-(Mo曱,·[2-(2-keto-1,3-tetrahydro-11-oxazol-3-yl)ethyl]-5,6 -Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-anthracepin-2'(1Ή)-one (46%) as a colorless solid: melting point I85-186°C; WNMRGOOMHtCDCls) δ 7.33 (dd, J = 7.8, 7.8 Hz, 1H), 7.18 (d, J = 7.3 Hz, 1H), 7.08 (dd, J = 7.3, 7.3 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.40 (s, 1H), 4.78 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H), 4.33-4.22 (m, 1H), 4.21-4.00 (m, 2H), 3.93-3.58 (m, 4H), 3.57-3.43 (m, 1H), 3.05-2.91 (m, 2H); 13C NMR (75 MHz, CDC13) 6 178.8, 161.8, 161.3, 158.7, 141.7, 132.4, 129.0, 124.1, 123.7, 120.0, 119.0, 108.3, 93 .2, 80.5, 72.5, 62.1, 57.7, 44.3, 41.7, 37.3, 29.0; MS (ES+) m/z 393.3 (M + 1). Example 9.4 Γ-(4-Acridine-2-ylindenyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b,]difuran-3,3,-吲哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 9, and carrying out irrelevant changes, use 5,6-dihydrospiro[benzo[7:5,4,7]difuran3,3'_ (1Ή)_ketone replaces 3-methylspiro[吱m[[f][2] benzisoxazole_5,3,吲哚]_2,(ιή) ketone, and 2-(4-(gas) Methyl)phenyl)pyridine substituted 2_(bromoindenyl)_5_(trifluoromethyl)

Two colorless solids: 217 219 143924-sp-20091127-4 • 624- 201020257 °C; 1H NMR (300 MHz, CDC13) δ 8.66 (d, J = 4.3 Hz, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.78-7.64 (m, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.25-7.11 (m, 3H), 7.00 (dd, J = 7.6, 7.6 Hz, 1H), 6.79 (d, J = 7.6 Hz, 1H), 6.49 (s, 1H), 6.42 (s, 1H), 5.00 (ABq, 2H), 4.85 (ABq, 2H), 4.52 (t, J = 8.6 Hz, 2H) , 3.09-2.87 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.9, 161.7, 161.2, 156.7, 149.6, 141.9, 138.9, 136.7, 136.4, 132.6, 128.6, 127.8, 127.3, 123.8, 123.4, 122.2 , 120.4, 120.1, 119.9, 118.8, 109.3, 93.2, 80.6, 72.3, 57.7, 43.8, 29.0; MS (ES+) m/z 447.1 (M + 1). Example 9.5 Γ-(thiaridin-2-ylindenyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲

Following the procedure as described in Example 9, and performing irrelevant changes, © using 5,6-dihydrospiro[benzo[l,2-b:5,4?']difuran-3,3,- θ| 哚]-2,(1Ή)-ketones are substituted for 3-methylspiro[furo[3,2_hung benzoisoxazole_5 3,_吲哚]_2, (1Ή) ketone, and 2 -(Gasylmercapto)pyrimidine substituted 2_(bromodecyl)-5-(trifluoromethyl)furan' to obtain Γ-(acridinyl fluorenyl)-5,6-dihydrospiro[benzo[i,2 -b : 5,4-b,]difuran-3,3'-responsible]-2'(anthracene)-one (84%) as a colorless solid: m.p. 2 -3 - 205 ° C; 4 NMR ( 300 MHz, CDC13) δ 8.68 (d, J = 4.9 Hz, 2H), 7.24-7.15 (m, 3H), 7.03 (dd, J = 7.5, 7.5 Hz, 1H), 6.75 (s, 1H), 6.73 ( d, J = 7.7 Hz, 1H), 6.42 (s, 1H), 5.22 (ABq, 2H), 4.89 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H), 3.07-2.93 (m, 143924) -sp-20091127-4 201020257 2H) , 13C NMR (75 MHz, CDC13) δ 178.0, 164.6, 161.6, 161.1, 157.4, 142.2, 132.9, 128.4, 123.7, 123.2, 120.5, 119.7, 119.7, 119.4, 108.7, 93.0 , 80.5.72.2, 57.7, 45.7, 29.0; MS (ES+) m/z 372.3 (M + 1). Example 9.6 Γ-('Bite-4-ylindenyl)_5,6-dihydrospiro[Benzo-like seven:5 4 b,]difuran_3 3,... 哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 9, and performing irrelevant changes, 5,6-dihydrospiro[benzo[i,2:7:5,4-1&gt;,]difuran-3,3,-丨哚丨哚]-2,(1Ή)-ketones are substituted for 3-mercaptospiro[, benzobenzoisoxazole_5 3,_吲哚]_2, (1Ή)-ketone, and 4- (gas-based) Mercaptopyrimidine-substituted 2_(bromomethyl)_5_(trifluoromethyl)furan-[is obtained by Γ-(orridin-4-ylmethyl)-5,6-dihydrospiro[benzo[l, 2-b : 5,4-b,] Difuro-3,3'-sideside-2'(1Ή)-_ (70%) ' is a colorless solid: mp 158-160. (: ; 1Η NMR (300 MHz, CDC13) δ 9.16 (s, 1H), 8.68 (d, J = 4.1 Hz, 1H), 7.30-7.15 Q (m, 3H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.79 (d, J = 7.7 Hz, 1H), 6.55 (s, 1H), 6.39 (s, 1H), 5.04 (ABq, 2H), 4.84 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 3.06-2.91 (m, 2H); 13C NMR (75 MHz, CDC13) &lt;5 177.9, 164.1, 161.8, 161.2, 158.6, 157.3, 141.5, 132.4, 128.7, 124.0, 123.7, 119.9 , 119.8, 118.9, 108.8, 93.1, 80.5, 72.3, 57.6, 44.9, 28.9; MS (ES+) m/z 372.3 (M + 1). Example 9.7 l'々 耕-2-ylmethyl)-5, 6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3^ 143924-sp-20091127-4 -626· 201020257 嗓]々'(ΓΗ)-ketone synthesis

And performing irrelevant changes, using 5,6-cyclone[benzo-like: seven:μ7·]difuran-by-dot]([Η) ketone replacement 3_A according to the procedure as described in Example 9. Base snail [snifeno[3,2-f][U]benzisoxazole-5,3,-啕哚]-2,(1Ή)-_, ❹ and 2-(hydroxymethyl) Pyridine substitution of 2-(bromomethyl)_5-(trifluoromethyl)furan' to obtain Γ-0-tough-2-ylindenyl)-5,6-dihydrospiro [stupid [i,2- b: 5,4-1)1]difuran-3,3-' 〇]-2'(1Ή)- Brewing J (27%), colorless solid: melting point i43-144°C; 4 NMR (300 MHz, CDC13) δ 8.64 (br s, 1H), 8.58-8.59 (m, 2H), 7.24-7.17 (m, 2H), 7.09-7.02 (m, 1H), 6.91-6.86 (m, 1H), 6.54 (s, 1H), 6.43 (s, 1H), 5.14 (ABq, 2H), 4,85 (ABq, 2H), 4.59-4.50 (m, 2H), 3.10-2.91 (m, 2H) ; 13 C NMR (75 MHz, CDC13) (5 177.9, 161.9, 161.3, 151.4, 144.2, 143.9, 143.8, 141.6, 132.7, 128.8, 124.0, 123.8, 120.0, 119.9, 119.0, 109.1, 93.2, 80.6, 72.4, ❹ 57.8, 43.8 , 29.0; MS (ES+) m/z 372.3 (M + 1). Example 9.8 Γ-[(7-Alkyl-1-benzofuran-2-yl)methyl]-5,6-dihydrospiro[ Benzo[l,2-b : 5,4-b,] Shouting voice] -2 (1Ή) '- one Synthesis of

143924-SD-20091127-4 -627- 201020257 Follow the procedure as described in Example 9 and perform irrelevant changes using 5,6-dihydrospiro[benzo[l,2-b ··5,4 -b']difuran-3,3'-indole]-2'(1Ή)-one substituted 3-mercaptospiro[吱,[3,2-f][l,2] benzisoxazole -5,3'-v?丨哚]-2,(1Ή)-ketone, and 2-(bromoindenyl)-5- is replaced with 2-(bromoindenyl)-7-fluorobenzofuran (Trifluoromethyl)furan to give 1'-[(7-fluoro-1-benzofuran-2-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3,-anthracene-2, (fluorenyl)-one (83%) as colorless solid: m.p. 192-193 ° C; 4 NMR (300 MHz, CDC13) (5 7.31-7.24 (m, 2H), 7.22-6.96 (m, 5H), 6.77-6.74 (m, 1H), 6.56 (s, 1H), 6.43 (s, 1H), 5.31-5.23 (m, 1H) ), 5.03-4.95 (m, 2H), 4.75-4.68 (m, 1H), 4.59-4.49 (m, 2H), 3.10-2.91 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.6, 161.8 , 161.2, 152.8, 147.8 (d, JC.F = 249.7 Hz), 141.9 (d, JC.F = H.3 Hz), 141.4, 132.7, 131.6 (d, JC-f = 3.2 Hz), 128.8, 123.9 , 123.7, 123.6, 120.1 (d, JC.F = 5.2 Hz), 119.0, 116.6 (d, JC.F = 3.9 H z), 110.8 (d, JC.F = 16.1 Hz), 109.0, 105.6 (d, JC.F = 2.1 Hz), 93.2, 80.4, 72.4, 57.7, 37.5, 29.0; MS (ES+) m/z 428.3 ( M + 1). Example 9.9 - (tata-3-ylmethyl)_5,6-dihydrospiro [benzo-like seven: 5 4-7,] difuran_3 3,_w 哚]-2' (1 ,Η)--the synthesis of the class

According to the procedure as described in Example 9 and the insignificant change was made, 5,6-monohydrospiro[benzo(10)7:5,4,7,]difuran·3 3,(9)哚]_2, (ιή) ) ketone replacement 3 methyl snail '[吱D南和[3,块U]Benzene 11th 嗤-5,3,-令朵]-2,(1Ή)-ketone, 143924-sp-20091127- 4 201020257 and using 3-(methyl-methyl) hydrazine to replace 2-(bromohydrazino)_5_(trifluoromethyl)furan' to obtain Γ-0荅 -3--3-ylmethyl)-5,6- Dihydrospiro[benzo[i,2_b:5,4-b']difuran-3,3W| 哚]-2'(1Ή)-one (13%) as a colorless solid: mp. 81. NMR; NMR NMR (300 MHz, CDC13) δ 9.18-9.14 (m, 1Η), 7.58-7.44 (m, 2H), 7.28-7.15 (m, 2H), 7.12-7.02 (m, 2H), 6.47 (s , 1H), 6.43 (s, 1H), 5.39-5.22 (m, 2H), 4.84 (ABq, 2H), 4.60-4.49 (m, 2H), 3.10-2.91 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 178.1, 161.9, 161.4, 158.4, 151.1, 141.6, 132.4, 129.0, 127.3, 126.0, 123.9, 123.8, 120.0, 119.9, 118.8, 109.6, 93.3, 80.6, 72.4, 57.8, 44.6, ® 29.0; MS (ES+) m/z 372.3 (M + 1). Example 9.10 Γ-[(2-keto-1,3-tetrahydrocarbazol-5-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b Synthesis of ']二吱喃-3,3Ί 嗓]-2'(1Ή)-®Ι

Using 5,6-dihydrospiro[benzo[i,2-b:5,4-b^furan-3,3W丨哚] according to the procedure as described in Example 9, and performing irrelevant changes -2, (1Ή)-ketone replacement 3-methyl snail [biting cation and yang cleavage benzoisoxazole _5,3, _ρ5丨哚]_2, (1Ή)_嗣, and using 5-gas hydrazine Substituting the oxazolidinone for 2-(bromohydrazinyl)-5-(trifluoromethyl)-anthracene to obtain l'-[(2-keto-1,3-tetrahydro&lt;»" sitting- 5-yl) fluorenyl]-5,6-dihydrospiro[benzo[l,2-b:5'4-7,]difuran_3,3,-吲哚]-2,(1Ή)-嗣(32%) as colorless solid: mp 197-198 ° C; 4 NMR (300 MHz, DMSO-d6) δ 7.58 (s, 1 Η), 7-37-7.29 (m, 1 Η), 7.26-7.20 (m , 1H), 7.19-7.13 (m, 1H), 7.09-7.01 (m, 1H),

143924-sp-20〇91127-4 •629- 201020257 6.49-6.39 (m, 2H), 4.98-4.75 (m, 2H), 4.74-4.66 (m, 1H), 4.54-4.45 (m, 2H), 4.15 -3.84 (m, 2H), 3.67-3.56 (m, 1H), 3.31-3.23 (m, 1H), 3.02-2.90 (m, 2H); 13C NMR (75 MHz, DMSO-d6) &lt;5 177.9, 177.6, 161.2, 160.6, 160.5, 158.3, 142.6 (2C), 132.2, 132.0, 128.7, 128.6, 123.5, 123.4, 123.0, 120.6, 120.5, 119.9, 119.0, 118.9, 109.7, 109.6, 92.5, 92.4, 79.8, 73.3 , 73.2, 72.1, 56, 8, 43.1, 42.7, 42.6, 828.4; MS (ES+) m/z 379.3 (M + 1) 〇 Example 9.11 oxy) phenyl]-5,6-dihydrospiro [benzo Synthesis of [l,2-b : 5,4-b,]difuran-3,3,-啕哚]-indole)-one

According to the procedure as described in Example 9, and performing an insignificant change, 5,6-dihydrospiro[benzo[i,2-b:5,47']di-n--3,3'-吲0|2,(1Ή)-ketone-substituted 3-mercapto-spiro[3,2-f][l,2]benzisoxazole-5,3,-吲哚]-2' (ΓΗ)-ketone, and replacing 2-(bromomethyl)-5-(trifluoromethyl)sole with 1-(benzyloxy)-3-(bromomethyl)benzene to obtain hydrazine-[ 3-(yloxy)-yl]-5,6-dihydrospiro[benzo[i,2-b: 5,4-b'] dim--3,3·-啕哚]-2, (1Ή)-ketone (82%) as colorless solid: m.p.: 66-68°C; &lt;5&gt;H NMR (300 MHz, CDC13) &lt;5 7.43-7.14 (m, 8H), 7.06-6.99 (m, 1H), 6.97 -6.87 (m, 3H), 6.81-6.75 (m, 1H), 6.48 (s, 1H), 6.43 (s, 1H), 5.10-5.00 (m, 3H), 4.85-4.75 (m, 1H), 4.84 (ABq, 2H), 4.56-4.47 (m, 2H), 2.98-2.88 (m, 2H); 1 3C NMR (75 MHz, CDC13) δ 177.9, 161.8, 161.3, 159.2, 142.1, 137.4, 136.6, 132.7, 129.9, 128.7, 128.6, 128.0, 127.5, 123.8, 123.4, 120.2, 119.9 (2C), 118.8, 114.0, 113.9, 109.3, 93.2, 80.5, 72.3, 70.0, 57.7, 44.0, 143924-sp-20091127-4 -630 - 201020257 29·0 ; MS (ES+) m/z 476.1 (Μ + 1). Ά ir*j y.iz. 14(1-methyl-1H-benzo-salt salin-2-yl)methyl]_5,6-dichlorospiro[benzo[12

According to the procedure as described in Example 9, and with irrelevant changes, 5,6-dihydrospiro[benzo(10)7:5,4-b1]difuran-3,3,-P?丨嗓] -2,(1Ή)-keto-substituted 3-methylspiro[吱,[3,2_f][i,2]benzoiso-p-oxazoid]_2, (1Ή)-ketone, and using 2-( Bromomethyl hydrazino) fluorenyl _m-benzo[d]imidazole substituted 2 (bromomethyl)-5-(difluoromethyl) succinate' obtained [-[(μ曱-benzimidazole _ 2_yl)methyl]_ 5,6-dihydrospiro[benzo[1,2-7:5,4-b,]dioxan-3,3,-4丨哚]-2·(1Ή) -ketone (70%) ' is a colorless solid: mp 244-246 ° C; iH NMR (300 MHz, CDC13) 5 7.95-7.86 (m, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.49- 7.40 (m, 2H), 7.32 (dd, J = 7.6, 7.6 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 7.07 (dd, J = 7.6, 7.6 Hz, 1H), 6.52-6.36 (m, 2H), 5.51 (ABq, 2H), 4.81 (ABq, 2H), 4.55 (t, J = 8.6 Hz, 2H), 3.92 (s, 3H), 2.99 (t, J = 8.6 Hz, 2H) ; MS (ES+) m/z 424.1 (M + 1). Example 9.13 1·-(2Η-benzotriazol-2-ylmethyl)-5,6-dihydrospiro[benzo[1,2-b: 5,4-b,]difuran-3,3 Synthesis of '-啕哚]-2'(1Ή)-ketone 143924-sp-20091127-4 -631 - 201020257

According to the procedure as described in Example 9, and the insignificant change was made, 5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3,-吲哚]-2,(1Ή)-ketone replaces 3-methylspiro[吱,[3,2-f][l,2]benzisoxazole-5,3,-吲哚]-2, (1Ή)-ketone, and 2-(bromomethyl)-5-(trifluoromethyl) substituted with 2-(carbomethyl)-2Η-benzo[d][l,2,3] azide ) 吱 ,, obtaining Γ-ΡΗ-benzotriazole_2_ylmethyl)_5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3 '-Ten]-2'(1Ή)-ketone (67%), colorless solid: melting point 102-105Χ: ; WnMRGOOMHz^DO^) ά 8.14-7.96(m,lH), 7.89-7.80 (m, 1H ), 7.53-7.44 (m, 2H), 7.42-7.34 (m, 1H), 7.33-7.26 (m, 1H), 7.17-7.10 (m, 1H), 7.10-7.02 (m, 1H), 6.58 (ABq , 2H), 6.41 (s, 1H), 6.19 (s, 1H), 4.77 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 2.89 (t, J = 8.6 Hz, 2H) ; MS (ES+) m/z 411.1 (M + 1) 〇 Example 9.14 2-[(2'-keto-5,6-dihydrospiro[benzo[12:5:5,7]]difuran_3,3 ,钊哚]_Γ(2Ή)_基)曱基] Synthesis of benzoyl benzoate

143924-sp-20091127*4 201020257 Change 3-曱 base snail [吱 并[3,2-卬1,2] benzisoxazole-5,3'-啕哚]-2' (1 condition)- _, and 2-(bromomethyl)-5-(trifluoromethyl)pyrene was replaced with 2-(bromo-mercapto)benzoate to obtain 2-[(Τ-keto-5, 6-Dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3·-吲哚]-Γ(2Ή&gt;yl)indolyl]methyl benzoate (79 %) as a colorless solid: 1 NMR (300 MHz, CDC13) δ 8.04 (dd, J = 7.7, 1.3 Hz, 1H), 7.43 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H), 7.38-7.29 ( m, 1H), 7.22-7.11 (m, 3H), 7.07-6.99 (m, 1H), 6.70 (d, J = 7.7 Hz, 1H), 6.55 (s, 1H), 6.43 (s, 1H), 5.52 -5.34 (m, 2H), 5.00 (d, J = 8.9 Hz, 1H), 4.74 (d, J = 8.9 Hz, 1H), 4.54 (t, J = 8.7 Hz, 2H), ❹ 3.95 (s, 3H) ), 3.08-2.94 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 178.2, 167.5, 161.8, 161.4, 142.3, 137.5, 132.8, 132.7, 131.4, 129.1, 128.8, 128.6, 128.0, 127.4, 126.5 , 123.9, 123.5, 120.2, 120.0, 119.0, 109.4, 93.3, 80.8, 72.4, 65.9, 57.9, 52.3, 42.4, 29.1, 15.3; MS (ES+) m/z 427.9 (M + 1). Example 9.15 3-[ (2'-keto-5,6-dihydrospiro[benzene [L, 2-b: 5,4-b,] two bite drink 3,3, -4 Shu throat] -1, (2Ή) - yl) methyl] phenyl methyl ester of Yue

According to the procedure as described in Example 9, and performing an insignificant change, 5,6-dihydrospiro[benzo[i,2_b:5,4-b,]difuran-3,3,-qiao ]-2,(1Ή), replacing 3-methylspiro-vectors [3,2_f][i,2]benzoisoxazole_5,3,_嗍哚]_2·(1Ή^one, and Displacement of 2(bromoindenyl)-5-(trifluoromethyl)anthranol with 3-(&gt; odorant decyl) benzoic acid phthalate to give 3-[(2,-keto-5,6-di Hydrogen snail [benzo[U-7:5,4-7,]difuran-3'3-吲哚]-1'(2'11)-yl)methyl]benzoic acid decyl ester (93%), Colorless solid: melt 143924-sp-20091127-4 -633 - 201020257 point 97-98 ° C (hexane / ethyl acetate); 4 NMR (300 MHz, CDC13) 5 8.04 (s, 1H), 8.02-7.96 ( m, 1H), 7.58-7.52 (m, 1H), 7.49-7.42 (m, 1H), 7.25-7.17 (m, 2H), 7.09-7.00 (m, 1H), 6.78 (d, J = 7.5 Hz, 1H), 6.56 (s, 1H), 6.45 (s, 1H), 5.16 (d, J = 15.7 Hz, 1H), 5.02 (d, J = 9.0 Hz, 1H), 4.89 (d, J = 15.7 Hz, 1H), 4.74 (d, J = 9.0 Hz, 1H), 4.60-4.52 (m, 2H), 3.93 (s, 3H), 3.13-2.96 (m, 2H) ; 13C NMR (75 MHz, CDC13) &lt; 5 178.1, 166.7, 162.0, 161.4, 141.9, 136.3, 132.8, 131.9, 130.9, 129.3, 129.2, 128.9, 128.4, 124.1, 123.7, 120.2, 120.1, 119.1, 109.2, 93.4, 80.7, 72.5, 57.9, 52.3, 43.9, 29.2 ; MS (ES+) m/z 428.1 (M+ 1) Example 9.16 4-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]dioxan-3,3,-W 嗓Synthesis of Γ(2Ή)-yl) fluorenyl] benzoic acid oxime ester

Follow the procedure as described in Example 9, and perform an insignificant change' using 5,6-monohydrospiro[benzo[ub:5,4-b,]difuran-3,3'-吲哚]- 2, (1Ή)-ketone replacement 3-mercapto snail [唉 并 [[ 幻 幻 幻 噚 噚 噚 噚 噚 噚 _ _ _ _ _ _ _ , , , , , , 并 并 并 并 并 并 并 并 并Substituting methyl benzoate for 2 (bromo mercapto (trifluoromethyl)) to give 4-[(2,-keto-5,6-dihydrospiro[benzo-like seven:54_b,] Difuran_3'34哚Η|(2Ή)-yl)methyl]benzoic acid methyl vinegar (95%) as a colorless solid: melting point 136-14 (TC; iH NMR (300 MHz, CDCl3) occupies 8 〇1讥j = 8 Ηζ, 2 Η), 739 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 7.4 Hz, 2H), 7.02 (dd, J = 7.4, 7.4 Hz, 143924-sp*20091127 -4 -634- 201020257

1H), 6.72 (d, J = 7.6 Hz, 1H), 6.48 (s, 1H), 6.44 (s, 1H), 4.99 (ABq, 2H), 4.84 (ABq, 2H), 4.54 (t, J = 8.6 Hz, 2H), 3.89 (s, 3H), 3.06-2.92 (m, 2H); MS (ES+) m/z 428.1 (M + 1). Example 9.17 Γ_[3_(yloxy)propyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,- 哚 哚]- 2·(1Ή)-ketone synthesis

&quot;Ο 5,6-dihydrospiro[benzo[i,2_b : 5,4-b']difuran-3,3, according to the procedure as described in Example 9, and with irrelevant changes -啕哚]-2'(1Ή)-ketone-substituted 3-methylspiro[, succinimide (3) benzoisoxazole _5,3,_ρ 哚]_2, (1Ή)-ketone, and benzyl Replacement of 2-(bromomethyl)-5-(trifluoromethyl)pyranyl with 3-bromopropyl ether to give Γ-[3-(decyloxy)propyl]_5,6-dihydrospiro[ Benzo[i,2-b:5,4-b']difuranium -3,3'_u ylide to WU'H)-ketone (89%) as a colorless solid: mp ii2-ii3 ° C ( Ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 7.35-7.27 (m, 6H), 7.14 (d, J = 6.0 Hz, 1H), 7.06-6.95 (m, 2H), 6.41-6.39 (m, 2H), 4.63 (AB, 2H), 4.54-4.48 (m, 4H), 3.94-3.80 (m, 2H), 3.54 (t, J = 6.0 Hz, 2H), 2.95 (t, J = 9.0

Hz, 2H), 2.07-1.99 (m, 2H); MS (ES+) m/z 428.1 (M + 1). Example 9.18 5'-Fluoro-l'-[(2R)-w-hydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b'] Synthesis of difuran-3,3'-吲哚]-2Χ1Ή)-one

A 143924-SP-20091127-4 -635 201020257

α' according to the procedure as described in Example 9, and performing an insignificant change, using 5·-fluoro-5,6-dihydrospiro [stupid [1,2 7:5,4-b,] 2 Furan-3,3,-anthracene-2'(1Ή)-ketone replacement 3-methylspiro[furo[3,2-ί][1,2]benzoiso-p-azole _5,3 '-嘀哚]-2'(1Ή)-ketone, and replacing 2-(bromoindenyl)-5-(three) with (r)-(tetrahydrofuran-2-yl) decyl 4-methylbenzenesulfonate Fluorinyl) oxime to give 5,-fluorotetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[7:5,4-b,]difuran-3,3, -W哚]-2'(1Ή)-one (60%) as a colorless solid: mp.: m.p., mp., mp, mp, mp, mp, mp, mp. 1H), 6.39 (s, 1H), 4.76 (ABq, 2H), 4.52 (t, J = 9.0 Hz, 2H), 4.28-4.20 (m, 1H), 3.89-3.69 (m, 4H), 2.98-2.95 (m, 2H), 2.10-1.63 (m, 4H); 13C NMR (75 MHz, CDC13) δ 178.0, 161.9, 161.2, 157.9, 138,7, 134.3, 120.0, 118.8, 115.1,114.8, 111.7, 111.4, 110.5, 93.3, 80.5, 72.4, 68.2, 58.0, 44.8, 29.0, 28.9, 25.7 ; MS (ES+) ra/z 382.1 (M + 1) 〇6,-f-group-1,-[(2R)-tetrahydrogen squeak. Nansi Methyl] 5 6 · Dichlorospiro [Benzene

C〇 The procedure described in Example 9A, and the implementation of the insignificant change 143924-sp-20091127-4 * 636 - 201020257 using 6'-fluoro-5,6-dihydrospiro[benzo[l,2- b: 5,4-b,]difuran-3,3·-吲哚]-2'(1Ή)-one substituted 3-mercaptospiro[吱,[3,2-f][U]benzo Iso-indole-5,3·-哚]-2'(1Ή)-one, and replacing 2-(bromomethyl) with (R)-(tetrahydrofuran-2-yl)methyl 4-mercaptobenzenesulfonate 5-(5-(trifluoromethyl)pyranyl, 6-fluoro-r-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l, 2-b: 5,4-b']difuran-3,3·-吲哚]-2·(1Ή)-one (47%) as colorless solid: m.p. 137-139°C (diethyl ether/hexane 1; NMR (300 MHz, CDC13) δ 7.08-7.03 (m, 1Η), 6.88-6.83 (m, 1H), 6.73-6.66 (m, 1H), 6.46 (s, 1H), 6.38 (s, 1H ), 4.74 (ABq, 2H), 4.52 (t, J = 9.0 Hz, 2H), β 4.25_4.2〇 (吼1H), 3.96-3.60 (m shoulder, 2.98 (t, J = 9.0 take 2H), 2.08-1 Guan 3H), 1.73-1.64 (m, 1H); 13C NMR (75 MHz, CDC13) δ 178.0,161.9,161.2, 128.1, 124.7, 120.0, 118.8, 109.5, 109.2, 98.8, 98.4, 93.2, 80.6 , 72.4, 68.3, 57.3, 44.8, 29.2, 28.9, 25.7 MS (ES+) m/z 382.0 (M + 1). Example 9.20 142-(2-methoxyethoxy)ethyl]_2,3_dihydrospiro[p-mero[2,3_g][1,4]benzodioxene-8,3 Synthesis of '-吲哚]-2'(1Ή)-ketone

According to the procedure as described in Example 9, and the insignificant change was made, 2,3-dihydrospiro[2,3 g][14]benzodioxene oxime was used] 2'(1Ή)-_Replacement of 3_methylspiro[c-buto[3,2_Ώ[1,2] benzisoxazole_5,3,_吲哚]-2'(1Ή)-ketone' Displacement of 2-(bromodecyltrifluoromethyl)furan with i-bromo-2-(2-methoxyethoxy)ethane to give 1,-[2-(2-decyloxyethoxy) 143924 -sp-20091127-4 -637- 201020257 Ethyl]-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene-8,3,-哚 哚] 々 '(ΓΗ)-ketone (65%), is a colorless solid · · melting point 9 〇-91. (: ; 4 NMR (300 MHz, CDC13) δ 7.32-7.20 (m, 1Η), 7.14-7.09 (m, 1H), 7.05-6.97 (m, 2H), 6.46 (s, 1H), 6.21 (s, 1H), 4.73 (ABq, 2H), 4.19-4.12 (m, 2H), 4.12-4.05 (m, 2H), 4.05-3.96 (m, 1H), 3.94-3.83 (m, 1H), 3.64-3.57 ( m, 2H), 3.51-3.44 (m, 2H), 3.32 (s, 3H) ; 13C NMR (75 MHz, CDC13) S 177.6, 155.2, 144.5, 142.5, 138.3, 132.3, 128.7, 123.7, 123.2, 121.2, 111.6, 109.2, 99.3, 80.0, 71.9, 70.4, 68.2, 64.5, 63.9, 59.0, 58.0, 402; MS (ES+) m/z 397.9 (M + 1). Example 9.21 2-mercapto-Γ-0» ratio Synthesis of pyridin-2-ylmethyl) snail [pf-pyrano[2,3-f][l,3]benzopyrazole-7,3,-throindole]-2'(1Ή)-one

Following the procedure as described in Example 9, and performing an insignificant change, 2-methylspiro[2,3-f][l,3]benzoindole*-pyrazole-7,3' -吲嗓]-2,(1Ή)-keto-substituted 3-methylspiro[吱,[3,2-f][l,2]benzed,#,5,3'-4, -2,(1Ή)-ketone' and replacing 2-(bromomethyl)-5-(trifluoromethyl)furan with 2-(bromomethyl)pyridine hydrobromide to obtain 2-methyl-indole- (pyridin-2-ylmethyl) snail [aceto[2,3·Π[1,3]benzohepta-7,3'-吲嗓]-2'(1Ή)-one (38%) , as a colorless solid: mp 249-250 ° C (ethyl acetate); 1H NMR (300 MHz, DMSO-d6) (5 8.63-8.59 (m, 1H), 7.95 (d, J = 8.6 Hz, 1H) , 7.85-7.70 (m, 2H), 7.38-7.31 (m, 1H), 7.27-7.1 (m, 3H), 7.02-6.95 (m, 1H), 6.85 (d, J = 7.8 Hz, 1H), 5.31 (d, J = 16.9 Hz, 1H), 4.96-4.84 (m, 3H), 2.67 (s, 3H); 13C NMR (75 MHz, DMSO-d6) &lt;5 143924-sp-20091127-4 -638 - 201020257 176.4, 170.2, 160.2, 155.7, 149.3, 148.5, 142.3, 137.0, 131.9, 128.8, 128.1,

123.4, 123.1, 122.7, 120.7, 119.5, 109.3, 108.4, 81.0, 57.4, 45.6, 20.1 ; MS (ES+) m/z 400.0 (M + 1) 〇Example 9.22 1 -[(5-Alkyl-1-曱-1-1H-P m-sial-2-yl) fluorenyl]-2-methyl snail [bito-and-[2,3-f][l,3]benzoxazole _7,3'-峋哚] -2'(ΓΗ)-ketone synthesis

- Ν &gt;-ch3

S

X according to the procedure as described in Example 9 and the insignificant change was made using methylspiro[吱,[2,3-f][l,3]benzopyrazole-7,3,-啕哚]-2,(1Ή)-鲷substituted 3-mercaptospiro[吱,[3,2-f][l,2]benzisoxazole-5,3W丨哚]-2,(1Ή)-嗣, and replacing 2-(bromoindenyl)-5-(trifluoromethyl)anthracene with 5-oxo-2-(ylmethyl)-1-methyl-1Η-imidazole hydrochloride, Obtained ι'_[(5-carbyl-1-methyl-1Η-imidazol-2-yl)methyl]-2-methylspiro[rudo[2,3-f][l,3]benzene Pyrimidine-7,3'-indole-2,(1Ή)-one (68%), as colorless solid: mp 177-178 ° C (hexane / ethyl acetate); 4 NMR (300 MHz, CDC13) δ 7.63 (dd, J = 8.6, 1.1 Hz, 1H), 7.47 (d, J = 7.9

Hz, 1H), 7.29-7.23 (m, 1H), 7.08-6.92 (m, 4H), 5.42 (d, J = 15.4 Hz, 1H), 5.08-5.00 (m, 1H), 4.85-4.74 (m, 2H), 3.67 (s, 3H), 2.51 (s, 3H); 13 C NMR (75 MHz, CDC13) δ 176.8, 169.6, 160.5, 149.1, 142.1, 141.8, 132.1, 129.1, 124.6, 123.7, 123.3, 122.5 , 119.6, 119.3, 110.7, 108.7, 81.3, 60.5, 58.2, 38.4, 31.2, 20.2; MS (ES+) m/z 437.0 (M + 1), 439.0 (M + 1). Example 9.23 143924-sp-20091127-4 -639-201020257 4-mercapto-1 __·tetrahydrofuran-2-yl)methyl)_4,7-dihydrospiro[benzophenone[5'6 Seven][1,4]«^井_8,3'_Dihydro 十果]_2,,3卿二_合合ch3

Following the procedure as described in Example 9, and performing an insignificant change, 4-methyl-2H-spiro [biting and [2,3 g][1,4]benzoindole_8 3,吲哚]_2,,3 (1 H'4H) One network replacement 3_曱 base snail [biting cum [3, 2 illusion to two] stupid and isoxazole _n 峋哚]-2' (1Ή)-net And replacing 4-(bromoindenyl)-5-(trifluoromethyl)anthran with 4-(methylhydrobenzenesulfonic acid) (tetrahydrofuran-2-yl) decyl ester to obtain 4 methyl Γ (((8) four Hydrogen bite °Nan-2-yl)methyl)-4,7-dihydrospiro[benzofuro[5,6_na,4]噚耕_8,3,_dihydroindole]-2 ',3(2Η)-dione (11%) as colorless solid: iH NMR (300 MHz, (CD3)2CO) δ 7.35-7.30 (m, 1 Η), 7.23-7.13 (m, 2H), 7.08- 6.99 (m, 1H), 6.75 (s, 1H), 6.35 (d, J = 10.1 Hz, 1H), 4.92-4.87 (m, 1H), 4.74 (d, J = 9.2 Hz, 1H), 4.45-4.44 (m, 2H), 4.31-4.20 (m, 1H), 3.97-3.62 (m, 4H), 3.33 (s, 3H), 1.95-1.66 (m, 4H) ; 13 C NMR (75 MHz, (CD3) 2 CO) 5 178.8, 178.7, 166.1, 158.4 (2C), 1453, 145.1, 141.5, 133.9, 133.7, 133.2, 130.6, 130.5, 125.6, 125.3 (2C), 125.1 (2C), 124.6, 124.3, 112.9, 112.7 , 111.6, 111.5, 99.2, 99.1, 82.0, 81.8 (2C), 79.6, 78.2, 77.9, 75.7, 69.4, 69.3, 69.1, 59.6, 59.5, 46.0, 45.8, 30.7, 30.4, 29.8, 29.4, 27.2, 27.1 ; MS (ES+) m/z 406.9 (M + 1). Example 9.24 3_Methyl_Γ_(,bipyridin-2-ylmethyl)spiro[吱,[3,2-f][l,2] benzisoxazole-5,3'-(f)哚] Synthesis of -2'(1Ή)-ketone 143924-sp-20091127-4 -640- 201020257

Following the procedure as described in Example 9, and carrying out a non-critical change, 2-(bromomethylcyclohexane was substituted for 2_(bromomethyl)-5-(trifluoromethyl)anthracene, and it was found that 3- Methyl-1'-(pyridin-2-ylindenyl) snail [bito-and-[3,2 f][1,2] benzisoxazole-5'3-&lt;嗓]-2' (1Ή )- Brewing I (24%), colorless solid: melting point such as -(4) it (acetic acid φ vinegar / hexane); 1 NMR (3 〇〇 MHz, CDC13) 5 8.58 (d, J = 6.0 Hz, 1 Η) , 7.75-7.69 (m, 1H), 7.75-7.69 (m, 1H), 7.52-7.46 (m, 2H), 7.23-7.11 (m, 3H), 7.01-6.96 (m, 2H), 6.85 (d, J = 6.0 Hz, 1H), 5.45-4.89 (m, 4H), 2.45 (s, 3H), 3C NMR (75 MHz, CDC13) δ 176.1, 164.0, 158.2, 155.3, 154.9, 149.3, 142.0, 137.3, 130.4 , 129.4, 123.7, 123.6, 123.0, 122.7, 121.5, 117.9, 109.9, 108.9, 108.0, 81.4, 56.4, 46.4, 9.8; MS (ES+) m/z 383.9 (M + 1) 〇Example 9.25 Methyl-1- 〇 咬 -3- ylmethyl) 卜 夫 [ [32_£][1,2] benzoiso (1 azole _5,3, _ M丨哚]-2' (l'H)- _ synthesis

According to the procedure as described in Example 9, and the insignificant change was made, 3-(bromomethylcyclohexane was substituted for 2 (bromomethyl) 5 (trifluoromethyl) smog, and 3-methyl was obtained. -1 '7-pyridinyl _3_ylmethyl) snail [吱二和[3 2幻[to]benzisoxazole-5,3-θ|嗓]_2 (1 H)-one (65%) 'Colorless solid: melting point 176 177 〇c (acetic acid 143924-sp-20091127-4 •641-201020257 ethyl ester / hexane); 4 NMR (300 MHz, CDC13) 5 8.71 (d, J = 3.0 Hz, 1H) , 8.56-8.54 (m, 1H), 7.81 (d, J = 6.0 Hz, 1H), 7.46 (d, J = 9.0 Hz, 1H), 7.35-7.30 (m, 1H), 7.23-7.11 (m, 2H ), 7.01-6.96 (m, 2H), 6.77 (d, J = 9.0 Hz, 1H), 5.28-4.81 (m, 4H), 2.44 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 176.2, 164.0, 158.1, 155.0, 154.9, 149.4, 148.8, 141.5, 135.1, 131.0, 130.4, 129.4, 124.0. 123.9, 123.8, 123.1, 117.9, 109.4, 108.9, 108.0, 81.3, 56.3, 41.9, 9.8; MS (ES+) m/z 383.9 (M + 1). Example 9.26 3-Methyl-r-[(2R)-rahydrofuran-2-ylindenyl]spiro[3,2-f][l,2] benzisoindole carbazole-5,3 '-嘀哚]-2'(1Ή)-Synthesis of steel

Following the procedure as described in Example 9, and carrying out an insignificant change, replacing (2-)bromoindolyl-5-(4-)bromobenzenesulfonic acid (R)-(tetrahydrofuran-2-yl)methyl ester (trifluoromethyl)anthracene to give 3-mercapto-1,-[(2R)-tetrahydrofuran-2-ylindenyl]spiro[[吱,[3,2-f][l,2]benzene Isoxazol-5,3'-indole]-2'(1Ή)-one (50%) as colorless solid: mp 134-135 ° C (ethyl acetate /hexane); 4 NMR (300 MHz , CDC13) δ 7.43 (d, J = 9.0 Hz, 1H), 7.32-6.93 (m, 5H), 4.94 (ABq, 2H), 4.36-4.28 (m, 1H), 4.06-3.73 (m, 4H), 2.42 (s, 3H), 2.14-1.77 (m, 4H); 13 C NMR (75 MHz, CDC13) &lt;5 176.8, 176.3, 164.0, 158.2, 154.8, 143.2, 142.6, 130.4, 129.3, 123.5, 123.3, 122.9, 117.9, 110.5, 109.6, 109.1, 107.9, 81.4, 813, 77.8, 77.5, 68.4, 68.3, 56.3, 56.2, 44.9, 44.6, 29.4, 28.5, 26.1, 25.6, 143924-sp-20091127-4 -642- (8) 201020257 9.8 ; MS (ES+) m/z 377.0 (Μ + 1). Example 9.27 5,6-Dimethyl-1 '-(tetrahydro-2 fluorene-&gt; gram-4-ylindenyl) snail [ι_benzopyran_3,3,_ρ5丨哚]-2' (1Ή), the 'cheng

I ❿ According to the procedure as described in Example 9, and performing irrelevant changes, use 5,6-dimethylspiro[1-benzopyran-3,3'-p?丨嗓]-2' ( 1Ή)- Brewing I to replace 3-methylspiro[吱,[3,2-f][l,2]benzoindole ρ-5,3'-&lt;嗓]-2'(1Ή)-鲷, and 2-(bromomethyl)-5-(trifluoromethyl)furan was replaced with 4-bromomethyltetrahydropyran to obtain 5,6-dimercapto-indole-(tetrahydro-2-indole) -pyran-4-ylmethyl)spiro[1-benzofuran_3,3,_峋哚]-2'(1Ή)-one (55%) as colorless solid: mp 199-201 ° C ( Ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) 5 7.32-7.27 (m, 1H), 7.14-7.12 (m, 1H), 7.05-7.00 (m, 2H), 6.91-6.89 (m, 1H),6,75 (s,1H),6,41 (s,1H),4.71 ® (ABq, 2H), 4.12-3.95 (m, 2H), 3.75-3.54 (m, 2H), 3.39-3.28 (m, 2H), 2.19-2.02 (m, 7H), 1.62-1.28 (m, 4H); 13C NMR (75 MHz, CDC13) δ 111.9, 159.1, 142.8, 138.5, 132.6, 129.4, 128.7, 125.8, 124.0 , 123.7, 123.2, 111.4, 108.5, 79.9, 67.4, 58.0, 46.0, 33.9, 30.8, 20.3, 19.3; MS (ES+) m/z 364.3 (M + 1). Example 9.28 Synthesis of 5,6-dimethyl-indole-(pyridin-2-ylindenyl)spiro[l-benzofuran-3,3'-indole]-2'(1Ή)-one 143924-sp -20091127-4 -643- 201020257

5,6-Dimethyl 4,-(tetrahydro-2H-pyran-4-ylindenyl)spiro[1-benzofuran was used according to the procedure as described in Example 9 and insignificantly changed. -3,3'-

啕哚]々'(ΓΗ)-ketone replacement 3-methylspiro[furo-P,2-f][l,2]benzisoxazole-5,3·-ν5丨哚]_2,(1Ή) -ketone, and replacing 2-(Aminomethyl)-5-(trifluoromethyl)anthracene with 2-(indiylthio)pyridine to obtain 5,6-dimercapto-indenylpyridin-2- Methyl) snail [1-benzoxaffran-3,3'-indole]-2,(1Ή)-one (76%), as colorless solid: mp 165-168 ° C (ethyl acetate / Hexane); iH NMR (300 MHz, DMSO-d6) &lt;5 8.67 (d, J = 6.0 Hz, 1H), 8.12-8.06 (m, 1H), 7.59-7.55 (m, 2H), 7.26-7.23 (m, 1H), 7.21-7.20 (m, 1H), 7.03-6.98 (m, 2H), 6.76 (s, 1H), 6.55 (s, 1H), 5.18 (s, 2H), 4.74 (ABq, 2H ), 2.13 (s, 3H), 2.01 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6) 5

177.5, 159.1, 154.0, 146.7, 142.6, 141.5, 138.3, 132.6, 129.1, 126.7, 124.5, 124.4, 124.1, 123.7, 123.5, 111.3, 109.7, 79.5, 57.8, 43.7, 20.2, 19.2; MS (ES+) m/ z 357.2 (M + 1) 〇Example 9.29 5_气基·6_methoxy 'r_(tetran-n-butyl-4-ylmethyl) snail [1_benzopyrene]-2, (ΓΗ ), the synthesis

Procedure, change, as described in Example 9 and performed irrelevant change 143924-sp-20091127-4 (8) -644 - 201020257 using 5-fluoro-6-methoxyspiro[1-benzofuran-3 ,吲哚]-2'(1Ή)-ketone-substituted 3-methylspiro[B-pyrano[3,2-f][l,2]benzisoxazole-5,3'-吲哚]-2Χ1Ή -ketone, and 2-(bromomethyl)-5-(trifluoromethyl)furan was replaced with 4-(bromomethyl)tetrahydropyran to give 5-fluoro-6-methoxy- Γ-(tetrahydro-2H-piperazin-4-ylindenyl)spiro[1-benzofuran-3,3W|哚]-2·(1Ή)-one (82%) as a colorless solid: 1H NMR (300 MHz, CDC13) 7.30 (ddd, J = 7.7, 7.7, 1.3 Hz, 1H), 7.16-7.00 (m, 2H), 6.89 (d, J = 7.8 Hz, 1H), 6.59 (d, J = 6.8 Hz, 1H), 6.38 (d, J = 10.0 Hz, 1H), 4.90 (d, J = 9.0 Hz, 1H), 4.65 (d, J = 9.0 Hz, 1H), 4.02-3.92 (m, 2H) , 3.85 (s, 3H), ® 3.76-3.51 (m, 2H), 3.35 (t, J = 11.5 Hz, 2H), 2.18-2.00 (m, 1H), 1.65-1.37 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.4, 157.3 (d, J = 1.7 Hz), 149.3, 149.1, 149.0, 146.1, 142.7, 131.9, 129.1, 123.7 (d, J = 49.0 Hz), 118.9 (d, J = 6.4) Hz), 110.3 (d , J = 21.7 Hz), 96.4, 80.7, 67.41, 67.39, 57.9, 56.4, 46.1, 33.9, 30.8, 30.7; MS (ES+) m/z 384.2 (M + 1). Example 9.30 5-Fluoro-6-methoxy-1'-{[5-(trifluoromethyl)pyran-2-yl]methyl}spiro[μbenzofuran-3,3'-吲哚]-2,(1Ή)-ketone synthesis

According to the procedure as described in Example 9 and the insignificant change was made, 5-fluoro-6-methoxyspiro-tl-benzofuran-3,3,吲哚]2ι(ΐΉ)-one was used to replace 3_曱基螺 [biting and [3,2-f][l,2] benzisoxazole _5 3, 吲哚]_2, (1Ή) ketone, obtained

143924-sp-20091127-4 base &gt; carboxy-2-yl]methyl} snail [1-benzofuran is a colorless solid: melting point 45-47 ° C; 4

• 645- 201020257 NMR (300 MHz, CDC13) δ 7.32 (dd, J = 7.8, 1.2 Hz, 1H), 7.20-6.98 (m, 3H), 6.77-6.73 (m, 1H), 6.61 (d, J = 6.6 Hz, 1H), 6.44-6.38 (m, 2H), 5.05 (d, J = 16.2 Hz, 1H), 4.96 (d, J = 9.3 Hz, 1H), 4.90 (d, J = 16.2 Hz, 1H) , 4.70 (d, J = 9.3 Hz, 1H), 3.87 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 176.8, 157.1 (d, J = 1.8 Hz), 151.8 (d, J = 1.4 Hz) ), 149.2, 149.1 (d, J = 12.3 Hz), 146.1, 141.5 (q, J = 42.6 Hz), 141.3, 131.6, 129.2, 124.0, 123.9, 118.7 (d, J = 265.4 Hz), 118.6 (d, J = 7.3 Hz), 112.6 (q, J = 2.8 Hz), 110.3 (d, J = 21.6 Hz), 109.1 (d, J = 25.1 Hz), 96.3, 80.4, 57.9 (d, J = 1.3 Hz), 56.4, 36.9; MS (ES+) m/z 433.9 (M+l). Example 9.31 Synthesis of 5,6-difluoro-indole-(acridin-3-ylmethyl)spiro[i_benzofuran_3,3,_ρ5丨哚]_2,(ιή)-one

According to the procedure as described in Example 9, and the insignificant change was made, 5,6-difluorospirobenzopyrano-3,3'·吲嗓]_2, (1Ή) ketone was used to replace the 3 fluorenyl group. Snail [吱嗔,[3,2-f][l,2]benzoindazin _5,3'-ι»5丨嗓]_2'(ιή)-ketone, and 3-(bromomethyl) Substituting a 2-pyridyl hydrobromide for the 2_(bromomethyl)-5-(trifluoromethyl)p-vector to obtain 5,6-difluoro-indole-(pyridine-3-ylmethyl)spiro[μ Benzofuran_3,3,_啕哚]_ 2·(1Ή)-one (57%) is a colorless solid: melting point (7) means it; lHNMR (3〇〇MHz, CD3OD) δ 8.98 (s, 1H) , 8.84 (d, J = 5.4 Hz, 1H), 8.67 (d, J = 8.4 Hz, 1H), 8.12 (dd, J = 8.1, 6.0 Hz, 1H), 7.37 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.26 (d, J = 6.9 Hz, 1H), 7.18 (d, J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 6.93 (dd, J = 143924-sp -20091127-4 -646- 201020257 10.5, 6.3 Hz, 1H), 6.76 (dd, J = 9.6, 7.8 Hz, 1H), 5.27 (s, 1H), 5.26 (s, 1H), 5.00 (d, J = 9.6 Hz, 1H), 4.83 (d, J = 9.6 Hz, 1H); MS (ES+) m/z 365.2 (M + 1). Example 9.32 5'6-Difluoro-1'-{[5_(Trifluoro Methyl)pyran-2-yl]methyl}spiro tl_benzene Synthesis of furan_3,3,_ 啕哚]-2·(1Ή)-ketone

According to the procedure as described in Example 9, and the insignificant change was made, 5,6-difluorospiro[1_benzopyrano_3,3'_P5-dot]_2'(1Ή)-one was used to replace 3 -methyl snail [吱,[3,2-in-1,2] benzisoxazole_5,3,_峋哚]_2, (1Ή), obtains 5 6_difluoro-Γ-{[ 5-(Trifluoromethyl)pyran-2-yl]methylindole [!_benzofuran_3,3W丨哚]_ 2'(1Ή)-ketone (64%) as a colorless solid: 4 NMR (300 MHz, CDC13) &lt;5 7.34 (dd, J = 7.5 Hz, 1H), 7.21-6.99 (m, 3H), 6.82-6.74 (m, 2H), 6.53-6.39 (m, 2H), 5.07 (d, J = 15.9 Hz, 1H), 4.98 (d, J = 9.3 Hz, 1H), 4.90 (d, J = 15.9 Hz, 1H)' 4.73 (d, J = 9.3 Hz, 1H) ; MS (ES+ ) m/z 422 (M + 1). Example 9.33 Synthesis of 6-methoxy-indole-indolepyridin-2-ylmethyl)_2H-spiro[benzofuran-3,3'-dihydroanthracene]-2'-one

According to the procedure as described in Example 9, and the insignificant change was carried out, 143924-sp-20091127-4 -647- 201020257 using 6-methoxyspiro[1-benzofuran-3,3 W丨哚]- 2·(1Ή)-keto-substituted 3-methylspiro[吱,[3,2-f][l,2]benzisoxazole-5,3'-thirsty]-2'(1Ή)- Ketone, and 2-(Molylmethyl)-5-(trifluoromethyl)furan was replaced with 2-(methyl-methyl acridine hydrobromide) to give 6-methoxy-indole-(pyridine-2 -ylmethyl)-2Η-spiro[benzofuran-3,3'-dihydroanthracene]-2'-one (67%) as colorless solid: m.p. 122-123 ° C; WNMRGOOMHz, CDC13) 5 8.56 (s, 1H), 7.63 (dd, J = 7.8, 7.8 Hz, 1H), 7.32-7.09 (m, 3H), 7.0 (dd, J = 7.5, 7.5 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.65 (d, J = 7.8 Hz, 1H), 6.52 (d, J = 2.1 Hz, 1H), 6.36 (dd, J = 7.8, 2.1 Hz, 1H), 5.18 (d, J = 15.9 Hz, 1H), 4.98 (d, J = 15.9 Hz, 1H), 5.00 (d, J = 8.7 Hz, 1H), 4.72 (d, J = 8.7 Hz, 1H), 3.74 (s, 3H); 13C NMR (75 MHz, CDC13) ¢5 177.6, 162.1, 161.5, 155.5, 149.4, 142.1, 137.0, 132.3, 128.7, 123.7, 123.6, 123.4, 122.7, 121.5, 120.8, 109.4, 107.5, 96.5, 80.4, 57.6, 55.5, 46.0; MS (ES+) m/z 359.4 (M + 1). Example 9.34 6-decyloxy-Γ-0»pyridin-3-ylmethyl)spiro[μbenzofuran_3, Synthesis of 3,_4哚]

Following the procedure as described in Example 9, and performing irrelevant changes,

143924-sp-20091127-4 -648- 201020257 Obtain 6-methoxy-indole-(pyridin-3-ylmethyl)spiro[1-benzofuran_3,3'-峋哚]-2' (1Ή )-ketone (63%) as colorless solid: m.p., i64-165 ° C; iHNMRGOOMHz, CDC13) &lt;5 8.56 (s, 1H), 8.55 (d, J = 3.9 Hz, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.33-7.13 (m, 3H), 7.03 (dd, J = 7.5, 7.5 Hz, 1H), 6.80 (d, J = 7.8 Hz, 1H), 6.61-6.51 (m, 2H) , 6.37 (dd, J = 8.4, 2.1 Hz, 1H), 5.08 (d, J = 15.6 Hz, 1H), 4.98 (d, J = 9.0 Hz, 1H), 4.86 (d, J = 15.6 Hz, 1H) , 4.72 (d, J = 9.0 Hz, 1H), 3.76 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 177.7, 162.1, 161.6, 149.3, 148.8, 141.5, 135.2, 132.4, 131.5, 128.8, 124.0 , 123.8, 123.7, 123.4, 120.5, ® 108.8, 107.5, 96.6, 80.4, 57.5, 55.5, 41.6; MS (ES+) m/z 359,4 (M + 1). Example 9.35 6-Methoxy-indole-(tetrahydro-2H-«strept-4-ylmethyl) snail [i_benzofuran_3,3,_P|| 哚]-2'(1Ή)- Ketone synthesis

Φ According to the procedure as described in Example 9, and the insignificant change is made, using 6-methoxyspiro[1-benzopyrene _3,3'-〃5丨嗓]-2, (1Ή) - Stir 1 replaces 3-methylspiro[吱,[3,2-f][l,2]benzisoxazole_5,3,_byside]_2,(ιή)-阙, and uses 4 -(Momotylmethyl)tetrahydro-2, argon-substituted 2-(bromomethyl)-(trifluoromethyl)pyran, to give 6-methoxy-indole-(tetrahydro-2-indole-pyran Tetylmethyl) snail [μbenzofuran_3,3,_吲&gt;]-2 (1Η)-one (84%) ' is a colorless foam; 1H NMR (3〇〇MHz, CDC13) δ 7.31 (dd, J = 7.5, 1.2 Hz, 1H), 7.15 (dd, J = 7.5, 1.2 Hz, 1H), 7.04 (dd, J = 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H) , 6.57 (d, J = 8.4 Hz, 1H), 6.53 (d, J = 2.4 143924-sp-20091127-4 -649- 201020257

Hz, 1H), 6.36 (dd, J = 8.4, 2.4 Hz, 1H), 4.93 (d, J = 9.0 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.03-3.94 (m, 2H) ), 3.77 (s, 3H), 3.80-3.30 (m, 4H), 2.21-2.05 (m, 1H), 1.74-1.38 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.8, 162.1, 161.5 , 142.7, 132.6, 128.7, 123.9, 123.3, 123.2, 120.8, 108.5, 107.5, 96.6, 80.6, 67.4, 67.3, 57.5, 55.5, 46.0, 33.9, 30.8, 30.7; MS (ES+) m/z 366.4 (M + 1). Example 936 Synthesis of 6-methoxy-indole-(tetrahydro-2H-fluoren-2-ylindenyl)spiro[1-benzofuran-3,3,-chattyanone]

Following the procedure as described in Example 9, and performing an insignificant change, 3-(3-benzofuran-3,3'-啕哚]-2'(1Ή)-one was used to replace 3- Ruthenyl snail [ρ 喃 并 [3,2-f][l,2] benzisoxazole _5,3' 吲哚]-2'(1Ή)-one, and 2-(bromo) Tert-yl)tetrahydro-2-indole-peripipene substituted 2-(bromoindenyl)-5-(trifluoromethyl) succinate to give 6-methoxy-indole-(tetrahydro-2 Η- shouting -2 - 曱 ) ) 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 1- 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 28 (dd, J = 7.5, 7.5 Hz, 1H), 7.20-6.98 (m, 3H), 6.66-6.49 (m, 2H), 6.41-633 (m, 1H), 4.99-4.91 (m, 1H), 4.74 -4.66 (m, 1H), 4.02-3.31 (m, 8H), 1.92-1.19 (m, 6H); MS (ES+) m/z 366.4 (M + 1). Example 9.37 Euyloxy)ykyl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxan 143924-sp-20091127-4 •650- 201020257 Synthesis of ene-8,3^啕哚]-2·(1Ή)-ketone

2,3-Dihydrospiro[N,3_β][1,4]benzodioxolene _8,3,_ 哚 哚]_ 2'(1Ή)-one (2.0 g, 6.8 mmoler) In a solution of anhydrous ν, Ν-dimethylformamide (45 ml), add sodium hydride (60% in mineral oil, '0.35 g' 8.8 mmol) in the oil. ). The mixture was stirred at ambient temperature for 1 Å and was then added with a portion of 4-benzyloxy benzene (2.2 g, 9.4 mM) followed by potassium iodide (0.06 g, 0.34 m). The mixture was stirred at ambient temperature for 16 hours&apos; and diluted with water (2 mL) and ethyl acetate (200 mL). The liquid layer was separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with brine (150 mL The residue was purified by column chromatography and eluted with a gradient of 25% to 35% of ethyl acetate in hexanes to give 1,-[4-(---) - Dihydrospiro[吱, p, p, 3-g] [l, 4] benzodioxanthene-8,3*-啕哚]-2·(1Ή)-_ (2.49 g, 75%) , as a colorless solid: mp 87-89 ° C; iHNMR (300 MHz, CDC13) &lt;5 7.45-7.24 (m, 7H), 7.24-7.12 (m, 2H), 7.05-6.92 (m, 3H), 6.84 -6.79 (m, 1H), 6.51 (s, 1H), 6.22 (s, 1H), 5.06-4.90 (m, 4H), 4.82-4.62 (m, 2H), 4.24-4.08 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.4, 158.4, 155.2, 144.6, 142.1, 138.3, 136.8, 132.3, 128.7 (2C), 128.6, 128.0 (2C), 127.5, 123.8, 123.3, 121.0, 115.2, 111.5, 109.3, 99.4, 80.2, 70.0, 64.5, 63.9, 58.0, 43.6; MS (ES+) m/z 492.0 (M + 1) ° Example 9.38 143924-sp-20091127-4 • 651- 201020257 Γ-[4-(Amber )Hanji]-5,6-dihydrospiro [benzoan from: 5,4,7], two pm3, called 丨嗓]-2, (ΓΗ)-ketone synthesis

DBn follows the procedure as described in Example 9.37 and performs an insignificant change using 5,6-milk-2H-spiro [this is a conjugated [6,5_b]pyran-3,3'-diox p 丨嗓 丨嗓 _2 _2 _2 _2 _2 _2 _2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2·(1Ή)-ketone, obtaining 144-(yloxy)-yl]_5,6-dihydrospiro[benzo[12-7: φ 5,4-7|]difuran-3,3'-〃?丨哚]-2'(1,11)-one (77%) as colorless solid: mp 169-170 〇C; XH NMR (300 MHz, CDC13) δ 7.45-7.13 (m, 9H), 7.05-6.91 (m, 3H), 6.86-6.79 (m, 1H), 6.46 (s, 1H), 6.43 (s, 1H), 5.06-4.94 (m, 4H), 4.83-4.75 (m, 1H), 4.73-4.66 (m, 1H), 4.59-4.50 (m, 2H), 3.09-2.89 (m, 2H); 13C NMR (75 MHz, CDC13) δ 177.9, 161.8, 161.3, 158.4, 142.1, 136.8, 132.8, 128.8, 128.6 (2C), 128.2, 128.0, 127.4, 123.8, 123.3, 120.3, 119.9, 118.9, 115.1, 109.2, 93.2, 80.6, 72.4, 70.0, 57.7, 43.6, 29.0; MS (ES+) m/z 476.0 (M+l 〇❹ Example 9.39 (8S)-r-[4-(decyloxy)-yl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxole Luyuanene-8,3'-啕哚]-Τ(Γ ) - one Synthesis of

According to the procedure described in Example 9, and performing irrelevant changes, make 143924-sp-20091127-4 -652-

(S 201020257 with (83)-2,3-dihydrospirophtho[2,3-§][1,4]benzodioxanthene-8,3,-noise]-2· (1Ή)-嗣 Replacement 3-methyl snail [bite and [3,2-hunt 1,2] benzoisoxazole-5,3,-啕哚]-2'(1Ή)-嗣, and use 2-benzyloxy vaporized benzyl substituted 2-(bromomethyl)-5-(trifluoromethyl) acetylate to obtain (8S)-l,-[4-(yloxy)hanyl]-2 ,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-嘀哚]-2,(1Ή)-one (95%) , as a colorless solid: m.p. 151-153. (: 4 NMR (300MHz, DMSO-d6) (5 7.45-7.23 (m, 8H), 7.18-7.14 (m, 1H), 7.05-6.97 (m, 4H), 6.53 (s, 1H), 6.06 (s, 1H), 5.07 (s, 2H), 4.86 (ABq, J = 27.9, 15.6 Hz, 2H), 4.73 (ABq, J = 39.9, 9.3 Hz, © 2H), </ RTI> </ RTI> </ RTI> <RTIgt; 122.9, 121.2, 114.9, 110.8, 109.4, 98.8, 79.4, 69.1, 64.1, 63.5, 57.2, 42.4; MS (ES+) m/z 491.8 (M + 1). Example 9.40 {5-[(2'-keto) -2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanthine _8,3, - indazol noise] -Γ (2Ή) - yl) methyl piperidine _2_ wind-yl} -carbamic acid tert-butyl brewing _ Synthesis of

According to the procedure as described in Example 9, and with irrelevant changes, 2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxene _8 was used. , 3.丨哚]]-2'(1Ή)-ketone replacement 3-methylspiro[吱,[3,2-f][i,2] benzisoxazole_5,3'_ 4Bumu]- 2(1 H)-ketone' and replace [2-(bromoindenyl)-5-(trifluoromethyl) with [5-(m-methyl)p-bito-2_yl]carbamic acid second-butyl ester ) 吱 ,, obtaining {5_[(2'-keto-2'3-dihydrospich-[2,3-g][l,4] benzodioxanthene_8,3, _吲哚]_ 143924-sp-20091127-4 -653- 201020257 1'(2Ή)-yl)methyl]pyridin-2-yl}amino decanoic acid tert-butyl ester (74%) as a colorless solid : melting point 238-239 ° C; iHNMRGOOMHiDMSO-de) δ 9.81 (s, lH), 8.30-8.27 (m, 1H), 7.79-7.73 (m, 1H), 7.73-7.66 (m, 1H), 7.31-7.24 (m, 1H), 7.20-7.14 (m, 1H), 7.12-6.99 (m, 2H), 6.52 (s, 1H), 6.06 (s, 1H), 4.89 (ABq, J = 22.9, 15.5 Hz, 2H ), 4.74 (ABq, J = 44.4, 9.3 Hz, 2H), 4.23-4.05 (m, 4H), 1.45 (s, 9H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.7, 154.6, 152.6, 151.8 , 146.9, 144.1, 141.8, 137.8, 137.2, 131.6, 128.7, 126.2, 123.6, 123.1, 121.1, 112.2, 110.8, 109.3, 98.8, 79.5, 79.3, 64.1, 63.5, 57.2, 27,9 ; MS (ES+) m /z 502.1 (M+ 1). Example 9.41 3-decyl-indole-[2-(trifluoromethyl)hanyl]spiro[吱,[3,2-f][l,2] benzisoxazole_5,3'_啕哚]ΚΙΉ)--the synthesis of ketone

Following the procedure as described in Example 9, and performing an insignificant change, 2-(trifluoromethyl) evolved benzyl was substituted for 2_(bromodecyl)-5-(trifluoromethyl)sole to obtain 3-methyl. Trifluoromethyl) aryl] succinyl[3,2-f][l,2]benzoindole-5,3'-吲哚]-2,(1Ή)-one (60 %): melting point 192-194 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) (5 7.73-7.70 (m, 1H), 7.66-7.57 (m, 2H), 7.50-7.48 ( m, 1H), 7.41-7.36 (m, 1H), 7.22-7.14 (m, 2H), 7.05-6.98 (m, 2H), 6.68-6.64 (m, 1H), 5.54-4.90 (m, 4H), 2.47 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 176.5, 164.1, 158.1, 155.0, 141.8, 133.3, 132.8, 130.4, 129.5, 143924-sp-20091127-4 -654- 201020257 127.7, 127.5, 127.4 , 127.3, 126.3, 126.1, 123.8, 123.1, 117.9, 109.6, 108.9, 108.0, 81.5, 56.4, 40.9, 9.8; MS (ES+) m/z 450.8 (Μ + 1). Example 9.42 3-mercapto-14 3-(Trifluoromethyl)pyridin-2-yl]methyl}spiro[吱,[3,2-f][l,2] benzisoxazole oxime]-2'(1Ή)- Ketone synthesis

Following the procedure as described in Example 9, and carrying out an insignificant change, 2-(carbylmercapto)-3-(trifluoromethyl) = pyridine was substituted for 2-(bromomethyl)-5- (Trifluoromethyl)furan to give 3-mercapto-indole-{[3-(trifluoromethyl)pyridin-2-yl]methyl} snail [furo[3,2-f][l,2 Benzoisoxazole-5,3'-throindole-2'(1Ή)-one (87%): melting point 221-222 ° C (ethyl acetate); 1H NMR (300 MHz, DMSO-dg) 5 8.66-8.64 (m, 1H), 8.21-8.18 (m, 1H), 7.75-7.72 (m, 1H), 7.54-7.49 (m, 1H), 7.29-7.20 (m, 2H), 7.10-7.07 ( m, 1H), 7.02-6.97 (m, 2H), 5.27 (s, 2H), 4.96 (ABq, 2H), 2.41 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 176.7, 164.4, 158.0, 155.7, 155.6, 153.1, 152.7, 143.7, 135.4, 135.3, 130.0, 129.7, 126.1, 124.5, 124.3, 123.5, 123.3, 123.1, 122.5, 117.9, 109.9, 108.9, 108.4, 81.7, 56.0, 42.8, 9.8; MS (ES+) m/z 451.8 (M+l) 〇 Example 9.43 Γ-[3-(Hydroxy)propyl]-2,3-dihydrospiro[吱,[2,3-g][l ,4] Synthesis of benzodioxanthene-8,3'-吲哚]-2'(1'11)-one 143924-sp-20091127-4 -655 - 201020257

〇d Following the procedure as described in Example 9, and performing an insignificant change, replacing 2-(bromodecyl)-5-(trifluoromethyl)furan with albino 3-bromopropyl ether and using 2,3 _Dihydrospiro[c-butyl[2,3-g][l,4]benzodioxanthene oxime]-2·(1Ή)-ketone replacement 3_methylspiro[吱,[3, 2-f][l,2]benzisoxazole-5,3,-W ® '•花]-2'(1Ή)-_ 'Get Γ_[3·(芊oxy)propyl]_2, 3 dihydrospiro [bito and [2,3-g][l,4] stupid and dioxo-enolene]_2, (1Ή)嗣 (94%): melting point π % C (ethyl acetate / Hexane); A NMR (300 MHz, CDC13) &lt;5 7.33-7.23 (m, 6H), 7.14-7.12 (m, 1H), 7.02-6.94 (m, 2H), 6.47 (d, J = 0.9 Hz , 1H), 6.18 (d, J -0.9 Hz, 1H), 4.70 (ABq, 2H), 4.47 (s, 1H), 4.18-4.08 (m, 4H), 3.96-3.78 (m, 2H), 3.53 ( t, J = 6.3 Hz, 2H), 2.01 (d, J = 6.6 Hz, 2H); MS (ES+) m/z 443.9 (M+l). Example 9.44 Synthesis of Ethyl Ethyl Acetate (2 Keto 2,3-monohydrospib- oxo-dioxanedioxene _8,3,-啕 哚]-1'(2Ή)-yl) Ethyl Acetate

According to the procedure described in Example 9 φ ’ and the insignificant change, 143924-sp-20091127-4

(S-656-201020257 Replacement of 2-(bromohydrazino)-5-(trifluoromethyl)furan with ethyl bromoacetate, and using 2,3-dihydrospiro[furo[2,3-g] [l,4]benzodioxanthene-8,3,-anthracene-2'(ΓΗ)-嗣substituted 3-methylspiro[wantane[3,2-叩,2]benzo Isoxazole-5, 啕哚]-2·(1Ή)-ketone' obtained (2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzene Dioxodecene-8,3'-θ丨哚]-1·(2Ή)-yl)ethyl acetate (90%): m.p. 58-59°C (ethyl acetate/hexane); iH NMR (300 MHz, CDC13) 5 7.29-7.23 (m,1H), 7.18-7.15 (m, 1H), 7.08-7.02 (m, 1H), 6.77-6.74 (m, 1H), 6.47 (s, 1H), 6.34 (s, 1H), 4.89-4.39 (m, 4H), 4.25-4.15 (m, 4H), 4.11-4.08 (m, 2H), 1.26 (t, J = ® 9.0 Hz, 3H) ; MS (ES+ m/z 381.8 (M + 1). Example 9.45 r-{[(4S)-2,2-_TLmethyl-1,3-dioxoindol-4-yl]methyl}-2,3- Synthesis of Dihydrospiro[吱,[2,3-笆][1,4]benzodioxolene-8,3,-吲哚]-2,(1,11)-one

According to the procedure as described in Example 9, and irrelevant changes were made, using (3)-(2,2-dimercapto-1,3-dioxoindol-4-yl)methyl 4-mercaptobenzenesulfonate Displace 2-(bromohydrazinyl)-5-(trifluoromethyl)Pf-amane and use 2,3-dihydrospiro[吱,[2,3-g][l,4]benzoic Oxygen-based alkenyl -8,3'-吲哚]-2'(1Ή)-ketone-substituted 3-mercaptospiro[吱,[3,2-f][l,2]benzisoxazole-5 , 3W丨哚]-2,(1Ή)-_, obtain 1,_{[(4S)-2'2-methyl_1,3_-oxoindol-4-yl]indenyl}-2,3 -Diazane snail [bite and [2,3-g][l,4]benzodioxanene_8,3,-蚓哚]-2,(1Ή)-one (98%): melting point 55-57 ° C (ethyl acetate / hexane); iH NMR (300 MHz, CDC13) (5 7.30-6.99 (m, 143924-sp-20091127-4 • 657-201020257 4H), 6.47-6.20 (m, 2H), 4.88-4.84 (m, 1H), 4.63-4.59 (m, 1H), 4.48-4.40 (m, 1H), 4.17-3.77 (m, 8H), 1.35-1.28 (m, 6H); MS ( ES+) m/z 410.1 (M + 1). Example 9.46 6-Methoxy-indole-(4-methoxybenzyl)_2,-keto-l,,2,-dihydrospiro[μbenzo Synthesis of furan-3,3'-啕哚]-5-carbonitrile

Following the procedure as described in Example 9, and performing irrelevant changes, replacing 2-(bromomethyl)-5-(trifluoromethyl)anthracene with methyl iodide and using 6-hydroxy-indole-(4-methyl) Oxyfluorenyl) 2,-keto-yl, 2,-dihydrospiro[p-benzofuran-3 3, fluorene]-5-carbonitrile displaces 3-mercaptospiro I; Oxazole-5,3,(9) 哚]-2'(1'H)-one, 6-methoxyl-l (4-methoxybenzyl)21-keto-r,2,dihydrospiro [1-Benzofuran_3,3,_吲哚]·5_indenecarbonitrile (62%): melting point 2〇7_2〇8&lt;t (ethyl acetate/e^); iHNMR (300 MHz, CDCl3)5 7.27-7.20 (m,3H), 7.10-6.99 (m, 2H), 6.90-6.83 (m, 4H), 6.56 (s, 1H), 5.07-4.74 (m, 4H), 3.90 (s, 3H), 3.78 (s, 3H), MS (ES+) m/z 412.9 (M + 1). Example 9.47 6-Methoxy-2'-indenyl 4, decapyridin-2-ylindenyl Hi,2, dihydrospiro-benzofuran_3,3'-indole-5-carbonitrile Synthesis 143924-sp-20091127-4 -658 - 201020257

The 2-(bromomethyl)pyridine hydrobromide was substituted for 2-(bromomethyl)-5-(trifluoromethyl)furan using the procedures described in Example 9, and the insignificant changes were made and used. 6-decyloxy-2,-keto-1,2,-dihydrospiro[1-benzofuran_3,3,_ 啕哚]-5-carbonitrile substituted 3-methyl snail And [Hungry benzoisoxazole _5, 10 P 弓木] (1 H)-ketone' to obtain 6-methoxy 2'-mercapto-1'-(ΐ7比定定_2· Methyl)_ι,,2,_ Dihydrospiro[1-benzofuran-3,3'-indole-5-indolecarbonitrile (80%): mp 187-189 Χ: (ethyl acetate / hexane ); 11^1^(3001^2, 匚〇(:13)(5 8.57-8.55 (111,111), 7.70-7.64 (m, 1H), 7.27-7.20 (m, 3H), 7.12-7.00 ( m, 3H), 6.91-6.89 (m, 1H), 6.55 (s, 1H), 4.97 (ABq, 2H), 3.90 (s, 3H); 13 C NMR (75 MHz, CDC13) δ 176.7, 165.8, 164.1 , 154.9, 149.6, 142.3, 137.1, 131.2, 129.4, 128.8, 123.7, 123.6, 122.9, 122.0, 121.7, 116.7, 109.8, 94.6, 81.2, 56.9, 56.3, 45.9 ; MS (ES+) m/z 383.8 (M + 1) o Stomach Example 9.48 6-Fluoro-Z-keto-indole-(acridin-2-ylindenyl)_r,2,-dihydrospiro tl_indigofuran_3,3, _ 朵]-5-carbonitrile synthesis

Following the procedure as described in Example 9, and performing an insignificant change, 143924-sp-20091127-4 -659-201020257 Replacement of 2-(bromomethyl) with 2-(bromomethyl)pyridine hydrobromide 5 (trifluoromethyl) oxime, and using 6-fluoro-2,-keto-1,2,-dihydrospiro[μbenzo-drink_3,3,_ 吲哚]-5- Nitrile replacement of 3-mercaptospiro[吱,[3,2-fKU] benzisoxazole_5,3L p5|11 wood]-2 (1 Η)-嗣' to obtain 6-fluoro-2' -嗣基-Γ-(ϊγ比 bit_2_ylmethyl)_r 2,_ _ II snail [1-benzopyran-3,3'-吲嗓]-5-carbonitrile (55%): Melting point i〇8_i〇9°c ; 1 η NMR (300 MHz, DMSO-d6) δ Ί.11-Ί.66 (m, 1H), 7.29-7.20 (m 3H) 7.15-7.03 (m, 3H), 6.93-6.90 (m, 1H), 6.79-6.76 (m, 1H), 5.26-4.85 (m, 4H); MS (ES+) m/z 371.9 (M + 1). Example 9.49 6-Fluoro-2'-keto-l'-[(2R)-tetrahydrofuranylmethyl]-Γ, 2,-dihydrospiro[丨benzofuran-3,吲哚]-5-甲Nitrile synthesis

Co' is replaced by the procedure described in Example 9 and the inconsequential change is used to replace 2 bromomethylmethyl 4-(methyl)benzenesulfonate (R)-(tetrahydrofuran-2-yl)methyl ester. -(Difluoromethyl)furan, and 3-methyl spiro was replaced with 6-fluoro-2-, keto-oxime, 2,-dihydrospirobenzofuran-3,3,-indole carbonitrile [吱 并[3,2-iKU]benzisoxazole-5,3 '哚]-2'(1Ή)-one, 6-fluoro 2,-keto group _i, _[(2R) _tetrahydrofuran-2-ylmethyl]-indole, 2'-dihydrospiro-benzofuran_3,3,_啕哚]_5-carbonitrile (34%): H NMR (300 MHz, CDC13) d 7.37-7.27 (m, 1H), 7.12-7.06 (m, 3H), 7.01-6.92 (m, 1H), 6.79-6.74 (m, 1H), 4.94 (ABq, 2H), 4.31-4.21 (m, 1H) ), 3.91-3.72 (m, 4H), 2.12-1.84 (m, 4H); MS (ES+) m/z 364.9 (M + 1). Example 9.50 143924-sp-20091127-4 201020257 6-Fluoro-2'-keto-1'-[2-(trifluoromethyl)benzyl]-Γ 2,-dihydrospiro flbenzofuran_3, Synthesis of 3'-吲哚]_5_曱carbonitrile

Following the procedure as described in Example 9, and performing an insignificant change, replacing 2-(bromomethyl)-5-(trifluoromethyl)anthracene with 2-(difluoroindenyl) &gt; And using 6-fluoro-2'-keto-1,2,-dihydrospiro[1-benzofuran-3,3,-indole-5-carbonitrile to replace 3-methylspiro[furan Benzo-isoxazole _5,3,吲哚]_ 2·(1Ή)-one, 6-fluoro-2'-keto·ι,-[2-(trifluoromethyl)benzyl] _r, 2L dihydrospiro[1-benzofuran-3,3'-indole]-5-carbonitrile (55%): mp 193-195t (ethyl acetate / hexane); iH NMR (300 MHz, CDC13) &lt;5 7,76-7.73 (m, 1H), 7.53-7.39 (m, 2H), 7.27-7.22 (m, 1H), 7.17-7.07 (m, 3H), 7.01-6.99 (m, 1H) ), 6.82-6 79 (m, 1H), 6.70-6.67 (m, 1H), 5.27-5.09 (m, 3H), 4.90-4.87 (m, 1H) ; MS (ES+) m/z 419.0 (M- 19). _ Example 9.51 6-Fluoro-2'-keto-1'-{[3-(trifluoromethyl)P than bite_2_yl]methyl br, 2, dioxaspiro[1 benzofuran Synthesis of -3,3'-啕哚]-5-carbonitrile

Following the procedure as described in Example 9, and carrying out irrelevant changes, 2-(methylmethyl)-3-(trifluoromethyl acridine was substituted for 2-(bromomethyl)-5 (three i 143924-SO-20091127-4 -661 - 201020257 mercapto), and using 6-fluoro-21-keto-oxime, 2·-dihydrospiro[ι_benzopyrene_3,3,_啕哚]-5-phthalonitrile replacement 3-mercapto snail [bito-and-[3,2-f][l,2] benzisoxazole_5,3,-吲嗓]-2'(1Ή) -ketone 'obtains 6-fluoro-2'-keto-oxime-{[3-(trifluoromethyl)p than bite_2_yl]methylΗ', 2'-dihydrospiro[1-stupid Pf-methane-3,3'-thetad]-5-carbonitrile (67%): mp 209-211 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, DMSO-d6) &lt; 5 8.65 (d, J = 6.0 Hz, 1H), 8.23 (d, J = 6.0 Hz, 1H), 7.58-7.54 (m, 1H), 7.42-7.40 (m, 1H), 7.31-7.23 (m, 3H ), 7.06-7.01 (m, 1H), 6.93-6.91 (m, 1H), 5.21 (s, 2H), 5.03 (s, 2H); MS (ES+) m/z 440.2 (M + 1). Example 9.52 4'-Bromo-indolyl-pentyl-2,3-dihydrospiro[V-dea-[2,3-g][i,4]benzodioxene-8J-吲哚]-2 Synthesis of '(1Ή)-ketone

Following the procedure as described in Example 9, and performing an insignificant change, 2-(bromomethyl)-5-(trifluoromethyl)trimole was replaced with 1-iodopentane and 4 bromo groups were used. -2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene_8,3,_啕哚]-2·(1Ή)-one substitution 3 - 曱 螺 [[c, [[3,2_f][i,2] benzisoxazole_5,3,_ 嘀哚]-2'(1Ή)-one, obtaining 4·-bromo-Γ- Pentyl 2,3-dihydrospiro[吱,[2,3-g][1,4]benzodioxolene-8,3·-吲哚]-2,(ΓΗ)-ketone (54%) as colorless solid: JH NMR (300 MHz, CDC13) (5 7.20-7.15 (m, 2H), 6.87-6.83 (m, 1H), 6.45 (s, 1H), 6.16 (s, 1H) , 4.89 (ABq, 2H), 4.20-4.11 (m, 4H), 3.85-3.59 (m, 2H), 1.72-1.67 (m, 2H), 1.38-1.25 (m, 4H), 0.92-0.85 (m, 3H) ; 13C NMR (75 143924-sp-20091127-4 -662-201020257 MHz, CDC13) δ 117.0, 156.4, 144.7, 144.5, 137.9, 130.13, 130.10, 126.9, 119.9, 118.1, 111.0, 107.5, 98.9, 76.8 , 64.4, 63.8, 59.3, 40.5, 28.9, 27.0, 22.3, 13.9; MS (ES+) m/z 443.9 (M + 1), 445.9 (M + 1) ° Example 9.53 3-[(2·-keto- 2,3-dihydrospiro[吱,[2,3-g][ Synthesis of l,4]benzoxanthene oxide-8,3|-W哚]-Γ(2Ή)-yl)hydrazino]benzoic acid vinegar

Following the procedure as described in Example 9, and carrying out irrelevant changes, the 2-(bromomethyl)-5-(trifluoromethyl)furan was replaced with decyl 3-bromomethylbenzoate and used 2,3-Dihydrospiro[,,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one substitution 3- Methyl spiro[furo[3,2-hungry 1,2]benzisoxazole-5,3'-吲哚]-2Χ1Ή)-one, 3-[(2'-keto-2,3) -Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3Μ丨哚]-Γ(2Ή)-yl)methyl]benzoic acid methyl φ ester (99%), as a colorless solid: m.p.: 89-97°C (ethyl acetate/diethyl ether); 1H NMR (300 MHz, CDCI3) δ 7.98-7.95 (m, 2H), 7.51-7.42 (m, 2H), 7.19-7.14 (m, 2H), 7.03-7.01 (m, 1H), 6.73-6.70 (m, 1H), 6.50 (s, 1H), 6.27 (s, 1H), 5.19-5.13 (m, 1H), 4.95-4.92 (m, 1H), 4.84-4.79 (m, 1H), 4.67-4.64 (m, 1H), 4.19-4.11 (m, 4H), 3.90 (s, 3H) ; 13C NMR (75 MHz, CDC13 ) δ 111.6, 166.7, 153.3, 144.7, 141.7, 138.4, 136.1, 132.3, 131.7, 130.8, 129.2, 128.9, 128.1, 124.0, 123.6, 120.9, 111.6, 109.2, 99.4, 80.2, 64.5, 63.9, 58.1, 52.3, 43.8, 2 9.7 ; MS (ES+) m/z 443.8 (M + 1). 143924-sp-20091127-4 -663-201020257 Example 9.54 1 [2 (2 methoxyethoxy)ethyl]methylspiro[吱,[3,2-f][l,2]benzo Synthesis of different 11th saliva-5,3'-吲哚]-2,(l,H)-ketone

Substituting 1-bromo-2-(2-methoxyethoxy)ethane for 2-(bromodecyl) 5 (three gas) according to the procedure as described in Example 9, and performing irrelevant changes Base) 唉 ' 'obtained 142_(2_曱 ethoxyethoxy)ethyl]_3 methyl snail [sniff «Nanhe [3'2-f] [l, 2] benzoiso P azole _5, 3, _py 哚]_2, (ΓΗ)__ (98%), as a colorless oil: 1H NMR (300 MHz, CDC13) 5 7.45-7.42 (m,1Η), 7.30-7.27 (m, 1Η), 7.14-7.07 (m, 2H), 7.01-6.94 (m, 2H), 5.09-5.06 (m, 1H), 4.85-4.82 (m, 1H), 4.08-3.98 (m, 2H), 3.84-3.80 (m, 2H) , 3.68-3.65 (m, 2H), 3.51-3.49 (m, 2H), 3.34 (s, 3H), 2.42 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 176.1, 163.9, 154.8, 142.8, 130.4, 129.2, 123.5, 123.3, 122.8, 117.9, 109.8, 107.9, 81.2, 72.0, 70.7, 68.6, 59.0, 56.3, 40.8, 30.9, 9.8; MS (ES+) m/z 394.8 (M + 1). Example 9.55 3-Methyl-indole-(3-methylbutyl) snail [r-[3,2-f][l,2] benzisoxazole-5,3'- sorghum]-2 Synthesis of '(1Ή)-ketone

143924-sp-20091127-4 •664- 201020257 Following the procedure as described in Example 9, and carrying out irrelevant changes, replacing 2-(bromomethyl)_5_ with 1-bromo-3-methylbutane Trifluoromethyl)pyran, to give 3-methyl-indole-(3-methylbutyl)spiro[furo[3 2 -^12] benzisoxazole-5,3W丨嗓]-2' (1'H)-S is the same as (71%) as a colorless solid: m.p. 135 </ </ RTI> </ RTI> hexane (hexane); 1H NMR (300 MHz, CDC13) δ 7.45-7.42 (m, 1 Η), 7.33-7.28 (m, 1H), 7.11-7.09 (m, 1H), 7.01-6.94 (m, 3H), 5.07 (d, J = 9.0 Hz, 1H), 4.82 (d, J = 9.0 Hz, 1H), 3.94-3.87 (m , 1H), 3.77-3.70 (m, 1H), 2.43 (s, 3H), 1.77-1.63 (m, 3H), 1.01-0.98 (m, 6H); 13 C NMR (75 MHz, CDC13) δ 175.7, 163.9, 158.3, Ref. 154.8, 142.5, 130.8, 129.3, 123.7, 123.1, 122.8, 117.9, 109.2, 108.9, 107.9, 81.2, 56.3, 39.1, 36.0, 26.0, 22.6, 22.4, 9.8; MS (ES+) m/z 362.8 (Μ + 1). Example 9.56 3-Methyl-indole-(pyroxy-2-ylindenyl) snail [Mun-[3,2-f][l,2] benzisoxazole-5,3,- 吲哚] -2'(1Ή)-ketone synthesis

Following the procedure as described in Example 9, and performing an insignificant change, the replacement of 2 (gaskylmethyl) ρ than ρ well (Newkome, GR et al, Syni/iesis, (1984) 8: 676) -(bromomethyl)-5-(trifluoromethyl)furan to give 3-mercapto-indolyl-7-tung-2-ylmethyl) snail [吱,[3,2-f][l, 2] Benzoisoxazole-5,3·-throindole]-2'(rH)-net (20%) 'is a colorless solid: melting point 170-173 ° C (nonanol/hexane); iHNMRQOO MHz, CDC13) δ 8.81 (s, 1H), 8.63-8.47 (m, 2H), 7.48-7.45 (m, 1H), 7.21- 6.91 (m, 5H), 5.34-5.29 (m, 1H), 5.16-5.06 ( m, 2H), 4.90-4.87 (m, 1H)} 2.44 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 176.2, 163.9, 158.1, 154.9, 151.0, 143924-sp-20091127-4 - 665 - 201020257 144.1, 141.7, 130.4, 129.4, 123.9, 123.1, 118.0, 109.6, 108.9, 107.9, 81.2, 56.4, 44.3, 9.8, MS (ES+) m/z 384.7 (Μ + 1). Example 9.57 Γ-[(3-Fluoroacridin-2-yl)methyl]-3-methylspiro[p-benzobenzoxazole-5,3'-啕哚]-2, (1Ή) -_ synthesis

Displacement of 2-(bromomethyl)-5-(trifluoromethyl)furan using 2-(carbomethyl)_3-fluoropyridine according to the procedure described in Example 9 and subject to insignificant changes 'According to 1·-[(3-fluoropyridin-2-yl)indolyl]-3-indolyl sulphate [3,2-f] [1,2] benzisoxazole-5, 3'-&lt;哚]-2'(1Ή)-one (52%) as colorless solid: mp 167-169°C (diethyl ether); 4 NMR (300 MHz, CDC13) δ 8.38-8.36 (m, 1 Η ), 7.47-7.37 (m, 2H), 7.27-7.18 (m, 3H), 7.10-7.08 (m, 1H), 6.99-6.94 (m, 2H), 5.29-5.14 (m, 3H), 4.88-4.85 (m, 1H), 2.44 (s, 3H); 13C NMR (75 MHz, CDC13) δ 176.0, 164.1, 158.4, 156.3, 154.8, 145.3, 143.0, 142.4, 130.3, 129.2, 124.4, 123.6, 123.5, 123.3, 122.9, 117.9, 109.7, 108.9, 107.9, 81.6, 56.4, 41.3, 9.8; MS (ES+) m/z 401.8 (M+l). Example 9.58 2-[(3-Mercapto-2'-oxaspiro[吱,[3,2-phan [1,2] benzisoxazole-5,3, 丨哚]-Γ(2Ή) Synthesis of methyl-methyl]-1,3-oxazol-4-carboxylate 143924-SD-20091127-4 -666- 201020257

Following the procedure as described in Example 9, and carrying out an insignificant change, 2-(bromomethyl)-5-(three) was replaced with 2-(methylmethyl), methyl azole-4-carboxylate Fluoromethyl)furan, 2-[(3-methyl-2'-oxo[[3-,][l,2] benzisoxazole-5,3'-called 哚]-1'(2Ή)-yl)decyl]-1,3-oxazole-4-carboxylic acid methyl ester (80%) as a colorless solid: mp 148-152 ° C (dioxane) ;iHNMROOOMHtCDCl〗 δ 8.23 (s, 1H), 7.48-7.45 (m, 1H), 7.30-7.27 (m, 1H), 7.13-7.11 (m, 1H), 7.06-6.95 (m, 3H), 5.20 ( s, 2H), 5.14-5.11 (m, 1H), 4.88-4.85 (m, 1H), 3.91 (s, 3H), 2.43 (s, 3H) ; 13C NMR (75 MHz, CDC13) &lt;5 175.8, 163.9, 161.2, 159.0, 158.2, 154.9, 145.3, 141.1, 133.5, 130.1, 129.6, 124.1, 123.2, 118.0, 109.3, 108.7, 107.9, 81.2, 56.3, 52.3, 37.5, 30.9, 9.8; MS (ES+) m/ z 431.8 (M + 1). n in 4-[(2·-keto-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxene _8,3ΐ·

,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, (75 ml) 143924-sp-20091127*4 -667· 201020257 In the solution, add sodium hydride (6〇% w/w dispersion in mineral oil, 0.72 g, 17.9 mmol) at o°c. . The solution was stirred at 〇t for 5 hours and methyl 4-(bromomethyl)benzoate (3.00 g, 131 mmol) was added. The solution was stirred at ambient temperature for 16 hours and additional sodium hydride (6 〇 % w/w dispersion in mineral oil '0.30 g, 7.5 mmol) and 4-(bromomethyl)benzoic acid A were added. Ester (0.50 g '2.2 mmol), and the mixture was stirred for 1 hour, dried and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate in a 25% to 50% gradient of hexane to give 4-[(2,-keto-2,3-dihydrospiro[吱喃[2,34[1,4]benzodioxanthene_8,3'_啕嗓]_1, (2,η)-yl)methyl]paraben oxime ester (4.51 g '86 %) 'Colorless solid: melting point i67-169 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) (5 8.00 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 7.4 Hz, 2H), 7.03-6.96 (m, 1H), 6.73-6.68 (m, 1H), 6.48 (s, 1H), 6.22 (s, 1H), 5.10 (d, J = 15.9 Hz, 1H), 4.92 (d, J = 8.9 Hz, 1H), 4.84 (d, J = 16.0 Hz, 1H), 4.65 (d, J = 8.9 Hz, 1H), 4.19- 4.04 (m, 4H), 3.87 (s, 3H) ; 13C NMR (75 MHz, CDC13) &lt;5 177.6, 166.6, 155.3, 144.7, 141.8, 140.9, 138.4, 132.2, 130.3, 129.8, 128.9, 127.3, 124.0 , 123.6, ^ 120.9, 111.5, 109.2, 99.5, 80.1, 64.5, 63.9, 58.1, 52.2, 43.9 ; MS (ES+) m/z 443.9 (M + 1). Example 9.60 14 (4-Mercaptophyrin - 2-yl)methyl]-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanene-8,3'-吲哚]-2' (1Ή)-ketone Synthesis 143924-sp-20091127-4 -668- (S) 201020257

In a suspension of sodium hydride (60% w/w dispersion in mineral oil, 0.48 g, 12 mmol) in N'N-dimethyl decylamine (10 ml), add 2 below ,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene_8,3,_蜊哚]_ 2·(1Ή)-one (2.95 g' 1 〇 莫 )). The reaction mixture was stirred for 3 minutes, and 4-benzyl-2-(azepine) whollen (2.71 g, 12 mmol) was added with potassium moth (〇.1 g, 0.60 mmol). ear). The reaction mixture was heated at 100 &lt;0&gt;C for 16 hours, allowed to cool to ambient temperature&apos; and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate / hexane (3 / 7) to give benzyl benzyl carbazol-2-yl) hydrazino]-2, 3- Hydrogen snail [吱〇南和[2,3-g][l,4] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one (0.75 g, 74%) , as colorless solid: mp 88-100 ° C; 1H NMR (mixture of diastereomers, 300 MHz, CDC13) δ 7.35-7.20 (m, 6H), 7.16-7.11 (m, 1H), 7.07- 7.00 (m, 2H), 6.48 (s, 1H), 6.25 (s, 0.5H), 6.20 (s, 0.5H), 4.90-4.80 (m, 1H), 4.64-4.57 (m, 1H), 4.22 -4.08 (m, 4H), 3.98-3.40 (m, 7H), 2.87-2.56 (m, 2H), 2.23-1.98 (m, 2H); MS (ES+) m/z 485.0 (M + 1). Example 9.61 (8S)-r-{[(2S)-4-Germanyloxalin-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-layer][1 ,4] Synthesis of benzodioxanthene-8,3'-嘀哚]-2'(1'11)-one 143924-sp-20091127-4 -669· 201020257

(1994) '38(5): 1033-1040) Displaces 4-nonyl-2-(chloroindenyl)morpholine and uses (8S)-2,3-dihydronole[2] , 3_g][1,4]benzodioxanthene _8,3,吲哚]-2'(1Ή)-one substituted 2,3-dihydrospiro[furo[2,3_g][1, 4] benzodioxanthene, sulphur-8,3'-tenth]-2'(1Ή)-ketone, obtained qing], 丨[(2S)_4_benzylnorfosin_2_yl] (S)-4-benzyl-2-(alkylmethyl)morpholine (T〇shiya, M. et al.) (4) with methyl}-2,3-dihydrospiro[pfuran[ 2,3_g][i,4]benzodioxanthene _8,3,_吲 ]]-2'(1Ή)-one (99%) : MS (ES+) m/z 485.0 (M + 1 Example 9.62 Synthesis of (1,H)-one by Γ-(4-Mosyl)-5,6-difluoro-spiro-benzofuran_3,3,_p5丨哚]_2

Following the procedure as described in Example 9, and performing an insignificant change, the 2-bromobenzyl bromide was substituted for 2-(bromomethyl)-5-(trifluoromethyl) cough, and 5,6-di was used. Snail [1-benzofuran_3,3,_吲哚]_2, (1Ή)-ketone replacement 3 methyl spirofudo[3,2-f][l,2] benzisoxazole _534哚]_2,(1Ή)__, obtain Γ(4bromo-yl)-5,6-difluorospiro[1-benzofuran_3,3,·啕哚]_2,(1Ή)__ ( 54%), light yellow oil: 1H NMR (300 MHz, CDC13) accounted for 7.51 (s, 1 Η), 7.48 (s, 1 Η), 7.23- 143924-sp-20091127-4 6? 〇 (S: 201020257 7.04 ( m, 5H), 6.82-6.77 (m, 2H), 6.50 (dd, J = 8.9, 8.9 Hz, 1H), 5.03-4.96 (m, 2H), 4.84-4.72 (m, 2H) ; MS (ES+) m/z 442.1 (M + 1), 444.1 (M + 1). Example 9.63 5,6-difluoro-indole-(3-methylbutyl)spirobenzofuran_3,3,吲哚]_2, (1Ή) synthesis of 嗣

Following the procedure as described in Example 9, and performing an insignificant change, replacing 2-(bromoindenyl)-5-(trifluoromethyl)anthracene with 1-bromo-3-mercaptobutane, and Displacement of 3-methylspiro[5,2-f][l,2] using 5,6-difluorospiro[1-benzofuran_3,3,- 哚 哚]-ΑΓΗ)-嗣Benzoisoxazole _5,3,_parallel]-2,(1Ή)-one, 5,6-difluoro-indole-(3-methylbutyl)spiro[1-benzofuran_3 3, _峋哚]_2, (1Ή)__ (96%), light yellow oil: 1H NMR (300 MHz, CDC13) (5 7.34 (t, J = 7.7 Ηζ, 1 Η), 7.16-7.04 (m, 2H), 6.93 (d, J = 7.8 Hz, 1H), 6.77 (dd, J = 10.3, 6.3 Hz, 1H), © 6.50 (t, J = 8.5 Hz, 1H), 4.95 (d, J = 9.1 Hz , 1H), 4.70 (d, J = 9.1 Hz, 1H), 3.88-3.67 (m, 2H), 1.72-1.60 (m, 3H), 1.01 (d, 6.2 Hz, 6H) ; 13C NMR (75 MHz, CDC13) δ 176.3, 156.6 (d, JC.F= ll.〇Hz), 151.1 (dd, JC.F= 248.1, 14.5 Hz), 145.6 (dd, JC.F= 241.3, 14.0 Hz), 142.3, 131.6 , 129.2, 123.8, 123.3, 111.5 (d, J = 20.5 Hz), 108.7, 99.9 (d, J = 22.3 Hz), 80.7, 57.7, 38.8, 36.0, 26.0, 22.4, 22.3 ; MS (ES+) m/z 344.4 (M + 1). Example 9.64 5, 6-Difluoro-indole-(pyridin-2-ylmethyl)spiro[1-benzofuran_3,3'_吲哚]_2'(1'H)_嗣143924-SD-20091127-4 -671 · The synthesis of 201020257

Following the procedure as described in Example 9, and performing an insignificant change, 2-(bromomethyl oxaridinium hydrobromide was substituted for 2-(bromomethyl)-5-(trifluoromethyl)p And use 5,6-difluorospiro[1-benzofuran-3,3,-啕哚]-2,(1Ή)-嗣 to replace 3-mercapto snail [[ p 并 [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ [ Azole _5,3,j丨哚]_2,(1Ή)-one, 5,6-difluoro-1,(pyridin-2-ylmethyl)spiro[1-benzofuran-3,3, -啕哚]- 2'(1Ή)-one (29%) as light yellow oil: 1 η NMR (300 MHz, CDC13) δ 8.58 (d, J = 4.1 Hz, 1H), 7.71 (ddd, J = 9.4, 7.7, 1.7 Hz, 1H), 7.31-7.22 (m, 3H), 7.15 (dd, J = 7.4, 0.9 Hz, 1H), 7.05 (ddd, J = 8.4, 7.5, 0.9 Hz, 1H), 6.94 (d, J = 7.8

Hz' 1H)' 6.79 (dd, J = 10.3, 6.3 Hz, 1H), 6.66 (dd, J = 9.2, 7.9 Hz, 1H), 5.23 (d, J = 15.9 Hz, 1H), 5.06-4.96 (m , 2H), 4.77 (d, J = 9.1 Hz, 1H); MS (ES+) m/z 365.3 (M + 1). Example 9.65 5,6-di-free-tetrahydro-2H-«strand_4_ylmethyl)spirobenzofuran_3,3,·ρ丨嗓丨嗓]~2,(1,Η)- Ketone synthesis

()) puff, 'and irrelevant changes, earth methyl) tetrahydro'2Η_pyranyl replacement 2-(bromomethyl)-5-(trifluoromethyl and 5'6·-I snail [1_Benzo-benzopyran-3,3,-θ丨哚]-2,(1Ή)-ketone-H-ketone set 143924-sp-20091127-4 201020257

Change 3-mercaptospiro[furo[3,2-f][l,2] benzisoxazole-5,3'-峋哚]-2'(1Ή)-one to obtain 5,6-di Fluorine-Γ-(tetrahydro-2-indole-piperazin-4-ylindenyl)spiro[1-benzofuran-3,3·-吲哚]-2·(1Ή)-one (32%), light Yellow oil: 4 NMR (300 MHz, CDC13) δ 7.34 (ddd, J = 9.1, 7.7, 1.5 Hz, 1H), 7.16-7.05 (m, 2H), 6.93 (d, J = 7.9 Hz, 1H), 6.78 (dd, J = 10.3, 6.3 Hz, 1H), 6.49 (dd, J = 9.1, 7.8 Hz, 1H), 4.95 (d, J = 9.0 Hz, 1H), 4.70 (d, J = 9.0 Hz, 1H) , 4.00 (dd, J = 11.6, 2.5 Hz, 2H), 3.75-3.56 (m, 2H), 3.37 (ddd, J = 14.0, 11.6, 2.3 Hz, 2H), 2.15-2.08 (m, 1H), 1.62 -1.41 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 176.8, 156.7 (d, ❹ Jc-f = 10.9 Hz), 151.1 (dd, JC.F = 248.4, 14.5 Hz), 145.6 (dd, JC_F= 241.4, 14.0 Hz), 142.6, 131.3, 129.3, 124.0, 123.7 (dd, JC.F= 6.1, 3.1 Hz), 123.5, 111.5 (d, JC.F= 20.4 Hz), 108.8, 100.1 (d, JC.F = 22.3 Hz), 80.9, 67.3, 57.7, 46.1, 33.8, 30.7; MS (ES+) m/z 372.1 (M + 1) 〇 Example 9.66 2-[3-(2'-keto-5, 6-Dihydrospiro[benzo[1,2-7:5,4-b,]difuran-3,3'-啕哚]-1' ( Synthesis of 2Ή)-yl)propyl]_ih-iso called 丨哚i,3(2H)-dione

Displacement of 2_(bromoindolyl)-5-(trifluoromethyl) with Ν-(3-bromopropyl) phthalimide according to the procedure as described in Example 9 and with irrelevant changes Mute, and replace 3-mercapto with 5,6-dihydrospiro[benzo[2-b:5,4-b,]difuran-3,3·-啕哚]-2(111)-one Snail [吱 卩 卩, 2_£][1,2] benzoiso 11 azole-5,3-ρ5ΐ ^]-2(lH)-iq . ^ # 2-[3-(2'-^ 1 .-5,6--t, ^ # [1,2-b :

143924-sp-20091127-4 •673- 201020257 5,4-b·]difuran-3,3·-啕哚]-Γ(2Ή)-yl)propyl]-1Η-isoindole-1,3 (2H)-Diketone (39%) as a pale yellow solid: m.p. </RTI> </RTI> </RTI> </RTI> </RTI> </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; J = 5.5, 3.0 Hz, 2H), 7.31-7.28 (m, 1H), 7.18 (dd, J = 7.4, 0.8 Hz, 1H), 7.04 (ddd, J = 8.4, 7.5, 0.8 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.58 (s, 1H), 6.40 (s, 1H), 4.94 (d, J = 9.0 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.53 (t, J = 8.6 Hz, 2H), 3.98-3.89 (m, 1H), 3.85-3.75 (m, 3H), 3.01 (ddd, J = 10.6, 8.4, 1.7 Hz, 2H), 2.20-2.10 (m , 2H) ; 13 C NMR (75 MHz, CDC13) 5 177.7, 168.1, 161.7, 161.2, 141.9, 134.0, 133.0, 131.9, 128.7, 124.0, 123.3, 123.2, 120.2, 119.9, 118.9, 108.2, 93.1, 80.4, 72.4, 57.6, 38.0, 35.7, 29.0, 26.8; MS (ES+) m/z 466.9 (M + 1). Example 9.67 lL{[5-(Benzyloxy&gt;pyridin-2-yl)indolyl} snail [snolo[3,2-e][2,l,3]benzoxadiazole-8, Synthesis of 3·-吲哚]-2,(1Ή)-ketone

Η7Η-Snail [Benzene biting and [4,5-magic [1,2,5&gt; et al. η8,3,-dihydro-mu]-2,-ketone (0.400 g, 1.4 m) In a solution of anhydrous ν, Ν-dimethylformamide (7 ml), add sodium hydride (6 〇 % w/w dispersion in mineral oil, 0.086 g) at o °c , 3.6 millimoles)' and the mixture was stirred for 2 minutes. Add 5 (benzyloxy)-2-(carbomethylcyclohexane (0.44 g, L9 mmol), and stir the reaction mixture at ambient temperature for 19 hours. Add potassium iodide (1 mg, catalytic amount) and The reaction mixture was stirred at 6 (TC for 2 hours, at ambient temperature for 43 hours, at 60 ° C for 7 hours, and at the ring 掊, 田 卞 卞 工 工 工 工 , , , , 。 。 。 。 。 。 。 。 。 Saturated gas &gt; 1 143924-sp-20091127-4 -674- 201020257 Aqueous chain solution (7 ml) and water (30 ml), and the mixture was extracted with ethyl acetate (3 χ 10 ml). Washed with water (2×20 mL) and brine (20 mL), dried over sodium sulfate. /2) Dissolution> was then triturated in hexane to give 1, _([5-(benzyloxy)acridin-2-yl]methyl} snail [吱,[3,2-e][2, l,3]benzoxadiazole_8,3,_&lt; 哚]-2,(1Ή)-one (0,034 g, 5%) ' is a pale yellow solid: melting point 2〇9-212. (: ; 1H NMR (300 MHz, CDC13) δ 8.36 (d, J = 2.7 Hz, 1H), 7.83 (d, J = 9.6 Hz, 1H), 7.50 (d, J = 8.7 Hz, 1H), ® 7.45-7.23 (m, 8H), 7.18 (d, J = 7.5 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H ), 6.92 (J = 7.8 Hz, 1H), 5.39 (d, J = 15.9 Hz, 1H), 5.27 (d, J = 9.6 Hz, 1H), 5.11 (s, 2H), 4.99 (d, J = 9.3 Hz, 1H), 4.87 (d, J = 15.9 Hz, 1H); 13C NMR (75 MHz, CDC13) δ 176.0, 163.0, 154.4, 148.3, 147.1, 144.9, 142.2, 137.8, 136.0, 129.8, 129.7, 128.7, 128.3, 127.6, 123.7, 123.6, 122.4, 122.3, 121.9, 119.3, 110.2, 107.0, 82.0, 70.4, 57.4, 46.0; MS (ES+) m/z 477.2 (M + 1). s Example 9.68 φ keto _2 ,3_Dihydrospiro[,,[2,3-g][l,4]benzodioxanthene-8,3,- 朵 ]]-Γ(2Ή)-yl) fluorenyl]benzene Synthesis of ethyl citrate

According to the procedure as described in Example 9.67, and the insignificant changes were made, 2,3-dihydrospiro[furo[[magic (1)^benzodioxene]8,3,_ΡΡ丨嗓] -2'(1Ή), replacing 7H-spiro [benzofuro[4,5_c][1,2,5]oxadiazole_8,3,_two 143924-sp-20〇91127-4 •675· 201020257 Argon 哚 哚]-2'-ketone, and replacing 5-(benzyloxy)-2-(carbomethyl)pyridine with ethyl 4-(bromohydrazinyl)benzoate to obtain 4-[(2, -keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3'-(tetra) 哚]-1, (2Ή)- Ethyl ethyl benzoate (95%) as a colorless solid: iHNMRpOOMHz 'CDClg) 5 8.03 (d, J = 8.4

Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 7.21-7.16 (m, 2H), 7.03 (t, J = 7.5 Hz, 1H), 6.72 (d, J = 7.5 Hz, 1H), 6.52 (s, 1H), 6.24 (s, 1H), 5.14 (d, J = 15.9 Hz, 1H), 4.95 (d, J = 9.0 Hz, 1H), 4.87 (d, J = 15.9 Hz, 1H), 4.67 (d, J = 8.7 Hz, 1H), 4.36 (q, J = 7.1 Hz, 2H), 4.22-4.19 (m, 2H), 4.15-4.12 (m, 2H), 1.38 (t, J = 7.1 Hz , 3H) ; MS (ES+) m/z 458.1 (M + 1). _ Example 9.69 2-[3-(--keto-2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxene _8,3,_ Synthesis of 峋哚]-Γ(2Ή)-yl)propyl]-1H-isoindole-l,3(2H)-dione

According to the procedure as described in Example 9.67, and the insignificant changes were made, 2,3-dihydrospiro[,,[2,3-g][l,4] benzodioxanthene-8 was used. , 3-吲哚]-2·(1Ή)-ketone replacement 7H-spiro [benzofuro[4,5-c][l,2,5] oxadiazole-8,3,-dihydroindole -2'-ketone, and replacing 5-(benzyloxy)-2-(chloromethyl)p-pyridinidine with N-(3-bromopropyl)-o-phenyleneimine to obtain 2- [3-(2'-keto-2,3-dihydrospiro[唉,[2,3-笆][1,4]benzodioxanthene-8,3^吲哚]-1 '(2'11)-yl)propyl]-111-iso-indole-1,3(2H)-dione (92%) ' is a pale yellow solid: 1 η NMR (300 MHz, CDC13) δ 7.85- 7.82 (m, 2Η), 7.74-7.69 (m, 2H), 7.29-7.24 (m, 1H), 7.15 (d, J = 7.2 143924-sp-20091127-4 676- 201020257

Hz, 1H), 7.08-7.00 (m, 1H), 6.87 (d, J = 7.8 Hz, 1H), 6.48 (s, 1H), 6.29 (s, 1H), 4.89 (d, J = 9.0 Hz, 1H ), 4.64 (d, J = 9.0 Hz, 1H), 4.18-4.10 (m, 4H), 3.94-3.77 (m, 4H), 2.19-2.10 (m, 2H). Example 9.70 (8S)-1 -[2-(2-decyloxyethoxy)ethyl]_2,3-dihydrospiro [bito-and-[2,3_g][i,4] benzodioxan Synthesis of octaene-8,3'-throat]-2'(1Ή)-ketone

(8S)-2,3-Dihydrospiro [snolo[2,3-g][l,4]benzodioxolene _8,3% 丨哚丨哚]-2'(1Ή) - Ketone (0.27 g, 0.9 mmol) in a solution of anhydrous N,N-dimercaptocaramine (15 mL). Add sodium hydride at ambient temperature (60% w/w in mineral oil) w dispersion '0.054 g, 1.4 mmol). The mixture was stirred at ambient temperature for 15 minutes and 1 -bromo-2-(2-methoxyethoxy)ethane (0.33 g &lt; The mixture was stirred at 6 (TC) for 6 h and concentrated in vacuo. Water (50 ml) was added to the residue, and the mixture was extracted with ethyl acetate.遽' and concentration in vacuo. The residue was purified by column chromatography eluting with 40% ethyl acetate in hexane to give (8S)-r-[2-(2-methoxyethoxy) Ethyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxene _8,3·_ 吲嗓]-2·(1Ή) -_ (0.31 g, 85%) as a colorless oil: NMR (300 MHz, CDC13) 5 7.32-7.20 (m, 1H), 7.15-7.08 (m, 1H), 7.05-6.96 (m, 2H), 6.46 (s, 1H), 6.21 (s, 1H), 4.73 (ABq, 2H), 4.20-4.04 (m, 4H), 4.05-3.83 (m, 2H), 143924-sp-20091127-4 -677· 201020257 3.80-3.69 (m, 2H), 3.64-3.56 (m, 2H), 3.51-3.44 (m, 2H), 3.32 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.5, 155.1, 144.5, 142.5, 138.2, 132.3, 128.6, 123.7, 123.2, 121.2, 111.5, 109.2, 99.3, 80.0, 71.9, 70.4, 68.1, 64.5, 63.9, 59.0, 57.9, 40.2 ; MS (ES+) m/z 397.9 (M + 1 Example 9.71 6'-[2-(2-methoxyethoxy) Ethyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,8'-[1,3]pyrazolo[5 ,4^]啕哚]-7'(6|11)-ketone synthesis

2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8 was used according to the procedure as described in Example 9.70, and irrelevant changes were applied. ,8'-[1,3]pyrimidin [5,4-e]吲哚]-7,(6Ή)-keto-substituted (8S)-2,3-dihydrospiro[[,3,3 -g][l,4] benzodioxanthene-8,3'-吲哚]-2'(1 ugly)-one, 6,-[2-(2-methoxyethoxy) Ethyl]-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8,8,-[1,3]pyrazolo[ 5,4-e]吲哚]-7,(6Ή)-one (37%): mp 156-158°C; 1H NMR (300 MHz, CDC13) 5 8.77 (s, 1H), 8.07 (d, J = 8.6 Hz, 1H), 7.32 (d, J = 8.6

Hz, 1H), 6.56 (s, 1H), 6.23 (s, 1H), 4.83 (ABq, 2H), 4.23-4.04 (m, 6H), 3.85-3.77 (m, 2H), 3.67-3.61 (m, 2H), 3.52-3.46 (m, 1H), 3.32 (s, 3H); MS (ES+) m/z 455.1 (M + 1). Example 9.72 6'-Azetidin-2-ylindenyl)-2,3-dihydrospiro[furo[2,3-g][i,4]benzodioxanthene-8,8' -[1,3] Synthesis of diazolo[5,4-eH丨哚]-7'(6Ή)-ketone 143924-sp-20091127-4 •678- 201020257

According to the procedure as described in Example 9.70, and irrelevant changes were made, 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-like VII, chlorpyrifos and [5,4-e] 吲哚]-7, (6,H)-ketone replacement (dip)-2,3-dihydrospiro[吱,[2,3_g][14] Benzodioxanthene·8,3,-吲哚]-2,(1Ή)-one, and 2-bromo-2 is replaced with 2-(bromomethyl)-pyridyl hydrobromide -(2-methoxyethoxy)ethane, 6L (p-biti-2-ylmethyl)-2,3-dihydrospiro[furo[2,3-g][l,4] Benzodioxanthene-8,8'-[1,3]pyrazolo[5,4-e]indole-7,(6Ή)-one (41%), as colorless solid: melting point 156 -158〇C ; 1H NMR (300 MHz, CDC13) δ 8.75 (s, 1H), 8.60-8.53 (m, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.69-7.61 (m, 1H) , 7.32-7.26 (m, 1H), 7.23-7.17 (m, 1H), 7.13 (d, J = 8.2 Hz, 1H), 6.56 (s, 1H), 6.30 (s, 1H), 5.17 (ABq, 2H ), 4.87 (ABq, 2H), 4.24-4.03 (m, 4H); MS (ES+) m/z 444.1 (M + 1). Example 9.73 ® 4',6'-Dimethoxy_1'-[ 2-(2-decyloxyethoxy)ethyl]-2,3-dihydrospiro[snolo[2,3-g][l,4] benzodioxanthene _8,3 · _ foetida indol] _2, (1, H), synthesis of

Using 4',6'-dimethoxy-2,3-dihydrospiro[吱,[2,3-g][l, according to the procedure described in Example 9.70, and insignificantly changing. 4] benzodioxanthene 143924-SP-20091127-4 -679- 201020257 ene-8,3'-啕哚]-2'(1Ή)-ketone replacement (8S)-2,3-dihydrospiro [吱[2,3-g][l,4]benzodioxanthene-8,3·-(9)哚]-2'(1Ή)-one, 4',6'-dioxine Γ-Γ-[2-(2-methoxyethoxy)ethyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Alkene-8,3'-啕哚]-2'(1Ή)-_ (80%), as colorless solid: mp 158-16 (TC; lUNMR (300 MHz, DMSO-d6) δ 6.43 (s, 1H) , 6.33 (d, J = 4.2 Hz, 1H), 6.20 (s, 1H), 6.06 (d, J = 4.2 Hz, 1H), 4.70-4.46 (m, 2H), 4.19-3.99 (m, 4H), 3.79-3.72 (m, 2H), 3.65-3.52 (m, 4H), 3.52-3.42 (m, 2H), 3.38-3.24 (m, 6H), 3.18-3.11 (m, 3H) ; 13C NMR (75 MHz , CDC13) δ 178.8, 162.0, 156.7, 155.6, 155.5, 144.7, 144.1, 137.6, 120.4, 110.9, 109.2, 98.8, 92.9, 89.2, 71.0, 70.4, 68.3, 64.4, 63.9, 59.0, 56.9, 55.6, 55.5, 40.3 ; MS (ES+) m/z 458.1 (M + 1). Example 9.74 4·, 6 '-Dimethoxy-r-(acridin-2-ylmethyl)_2,3_dihydrospiro[吱3[g][1,4] Bento-oxetene-8,3 Synthesis of '-θ|嗦]-2,(1Ή)-ketone

According to the procedure as described in Example 9.70, and with irrelevant changes, 4',6'-dimethoxy-2,3-dihydrospiro[吱3[,4]benzo[ Oxygen decene-8,^ 哚]-2'(1Ή&gt;ketone replacement foot)_2,3_2^^^-dihydrospiro[吱,[2,3-g][l,4]benzene Oxygen

Oxy-Ι'-Ο»bipyridin-2-ylmethyl)_2,3·dihydrospiro' and 2-(bromomethyl)pyridylethoxy)ethane are used to obtain 4,6,- Dimethyl bromo[2,3-g][l,4]benzodioxane 143924-sp.20091127-4 201020257 urethane-8,3·-々哚]-2'(1Ή)-ketone (78%) as colorless solid: mp 187-188 °C; 'H NMR (300 MHz, DMSO-d6) 5 8.59-8.34 (m, 1H), 7.86-7.66 (m, 1H), 7.44-7.19 ( m, 2H), 6.51-6.32 (m, 1H), 6.32-6.14 (m, 3H), 5.17-4.80 (m, 2H), 4.79-4.50 (m, 2H), 4.25-3.95 (m, 4H), 3.66 (s, 3H), 3.61 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.7, 162.0, 156.7, 155.8, 155.6, 149.4, 144.3, 144.2, 137.7, 137.1, 122.7, 121.5, 120.3, 111.1 , 108.9, 98.9, 93.1, 89.5, 64.5, 63.9, 57.1, 55.6, 46.2; MS (ES+) m/z 447.1 (M + 1). Example 9.75

6-(2-decyloxyethoxy)-r_[2-(2-methoxyethoxy)ethyl]spirobenzofuran-3,3'-thirsty]-2'(1Ή) -ketone synthesis

According to the procedure as described in Example 9.70, and with irrelevant changes, use 6-(2-methoxyethoxy) spiro[μbenzopyran_3,3,_啕哚]_2, (1Ή ) ketone-substituted (8S)-2,3-dihydrospiro[吱-dioxandoxanene-8,3, 哚 哚]-2'(1Ή)-ketone' to obtain 6-(2-methoxy Ethyloxy)_Γ_[2_(2-methoxyethoxy)ethyl]spiro[1-benzofuran-3,3,-吲哚]_2, (ι,Η)-ketone (94%) , as colorless oil: 1 NMR (300 MHz, DMSO-d6) δ 7.32-7.27 (m, 1H), 7.12 (d, J = 7.2 Hz, 1H), 7.07-6.98 (m, 2H), 6.85 (d, J = 8.7 Hz, 1H), 6.76 (dd, J = 8.7, 2.6 Hz, 1H), 6.32 (d, J = 2.6 Hz, 1H), 4.78 (ABq, 2H), 4.08-3.88 (m, 4H), 3.82-3.74 (m, 2H), 3.68-3.59 (m, 4H), 3.52-3.47 (m, 2H), 3.37 (s, 3H), 3.34 (s, 3H) ; MS (ES+) m/z 414.1 ( M + 1) 〇 143924-sp-20091127-4 -681 - 201020257 Example 9.76 5-(2-methoxyethoxy Η'_[2_(2. methoxy &amp; ethoxy)ethyl] snail ^ Synthesis of benzopyrene-3,3'_吲哚]-2,(1Ή)-ketone

Displacement with 5-(2-methoxyethoxy)spirobenzofuran-3,3,啕哚] 2,(1Ή) ketone according to the procedure as described in Example 9.70, and with irrelevant changes ( 8S)-2,3-Dihydrospiropyrene and [2,3_g][1,4]benzodioxanthene_8 3,_啕嗓]-2'(1Ή)-ketone' obtained 5 -(2-methoxyethoxy)_Γ_[2_(2-decyloxyethoxy)ethyl]spiro[1-benzofuran-3,3,-〃?丨哚]-2, (1Ή )-ketone (80%) as colorless oil: 1 NMR (300 MHz, DMSO-dg) δ 7.31-7.27 (m, 1 Η), 7.15-7.10 (m, 1H), 7.06-6.99 (m, 2H), 6.63-6.58 (m, 1H), 6.56-6.53 (m, 1H), 6.42-6.36 (m, 1H), 4.81 (ABq, 2H), 4.11-4.02 (m, 2H), 3.83-3.76 (m, 2H) ), 3.75-3.70 (m, 2H), 3.69-3.54 (m, 4H), 3.52-3.45 (m, 2H), 3.43 (s, 3H), 3.33 (s, 3H) ; MS (ES+) m/z 414·1 (Μ+1). Example 10 1-(嗒耕-4-ylindenyl)-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3,3,-吲哚]-2 '(ΓΗ)-ketone synthesis

143924-sp-20091127-4 •682· 201020257 on 5,6-dihydro-2H-spiro[benzofuro[6,5-7]furan-3,3^indoline]_2,-one (0.20克 '0.72 mmol) and 嗒____ methanol (0.08 g, 〇J2 mmol) in a stirred suspension in anhydrous tetrahydrofuran (5 ml), add butyl at 〇t: Phosphine (0.27 ml, U mmol) followed by N,N,N,,N, tetramethylazodicarbamide (0.19 g, 1.1 mmol). The mixture was stirred at 〇t&gt;c for 15 minutes and at ambient temperature for 64 hours. Saturated aqueous ammonium carbonate solution (10 ml) was added, and the mixture was extracted with ethyl acetate (4×100 ml). The combined organic solution was washed with water (2×60 ml), brine (1 mL), dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography (hexane/ethyl acetate, from 1:1 to 1:3) to give the s. Stupid [i,2-b : 5,4-b'] two biting -3,3'-p 嗓]_

2'(1Ή)-嗣(0.03 g '11%): melting point 187-189 ° C; iHNMROOOMHz 'CDClJ δ 9.25-9.16 (m, 2H), 7.44-7.39 (m, 1H), 7.29-7.21 (m, 2H), 7.14-7.07 (m, 1H), 6.74-6.69 (m, 1H), 6.47 (s, 1H), 6.44 (s, 1H), 5.00 (ABq, 2H), 4.85 (ABq, 2H), 4.60 -4.52 (m, 2H), 3.11-2.93 (m, 2H) &gt; 13C NMR (75 MHz, ❿ CD3OD) δ 178.1, 162.1, 161.4, 151.3, 150.7, 141.0, 135.5, 132.5, 129.0, 124.7, 124.5, 124.3, 120.2, 119.5, 118.7, 108.4, 93.4, 80.6, 72.4, 57.7, 41.0, 29.0; MS (ES+) m/z 372.3 (M + 1); Example 11 Γ-[(2-Chloro-1,3) -pyrazol-5-yl)methyl]spiro[N-[2,3-f][l,3]benzodioxol-7,3'-W哚]-2, (1Ή) - the synthesis of the class

143924-sp-20091127-4 -683 - 201020257 A mixture of 2-bromopyrazol-5-methanol (0.80 g, 4.12 mmol) in ruthenium dichloride (10 mL) was refluxed for 3 h. The mixture was evaporated to dryness and dried in vacuo. The residue was redissolved in 2-butanone (15 mL), followed by the addition of carbonic acid (2.61 g, 8.0 mmol) and spiro[2,3-f][l,3]benzodiox. Wuyuanne-7,3·-Linghuao]-2'(1Ή)-ketone (1.12 g, 4.0 mmol). The reaction mixture was refluxed for 16 hours then concentrated to dryness in vacuo. The residue was dissolved in ethyl acetate (200 mL) and washed with water (5 mL) The organic phase was dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by flash chromatography using EtOAc EtOAc (EtOAc: EtOAc) [ρ夫π南和[2,3-f][l,3] stupid and dioxynene _7,3'-吲哚]-2,(1Ή)-one (0.70 g, 38%), Colorless solid: 1H NMR (300 MHz, CDC13) δ 7.58 (s, 1 Η), 7.30 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.22-7.17 (m, 1H), 7.09 (ddd, J = 7.5, 7.5, 0.9 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.52 (s, 1H), 6.09 (s, 1H), 5.90-5.86 (m, 2H), 5.16-5.08 ( m, 1H), 4.97 (d, J = 15.9 Hz, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H) ; MS (ES+) m/z 413.0 ( M + 1), 415.0 (M + 1). Example 11.1 1'-{[2-(didecylamino)-l,3-oxazol-5-yl]methyl} snail [吱,[2,3-f][l,3] benzo Synthesis of Dioxolene-7,3 W丨哚]-2'(1Ή)-ketone

Under nitrogen, in a sealed tube, Γ-[(2-carbyl-1,3-, pyrazol-5-yl)indolyl] snail [furan P,3-f][l,3] And dioxolene-7,3'-,5丨哚]-2'(1Ή)-one (0.10 143924-SP-20091127-4 - 684- (S) 201020257 g, 0.24 mmol) in N In a solution of N-dimethylformamide (5 ml), 2M dimethylamine (2.0 mL, 4.0 mmol) in THF. The reaction mixture was heated at 120 ° C for 16 hours. The reaction was quenched with water and then extracted with ethyl acetate (2 &lt The combined organic solution was dried over sodium sulfate, filtered, and concentrated to dryness. The residue was purified by flash chromatography using '30% ethyl acetate in hexane to give Γ-{[2-(dimethylamino)-1 1,3-oxazol-5-yl]methyl Tired [2,3-f][l,3]benzodioxol-7,3,-吲哚]-2'(1Ή)-one (0.08 g, 76%), Colorless solid: melting point 200-202. (:; ❹ 1H NMR (300 MHz, CDC13) 5 7.27 (ddd, J = 7.5, 7.5, 0.9 Ηζ, 1 Η), 7.20 (s, 1H), 7.15 (d, J = 7.5 Hz, 1H), 7.08- 6.95 (m, 2H), 6.51 (s, 1H), 6.14 (s, 1H), 5.91-5.84 (m, 2H), 5.05 (d, J = 15.6 Hz, 1H), 4.93 (d, J = 9.0 Hz , 1H), 4.84 (d, J = 15.6 Hz, 1H), 4.65 (d, J = 9.0 Hz, 1H), 3.06 (s, 6H) ; 1 3 C NMR (75 MHz, CDC13) (5 177.2, 172.0 , 156.1, 149.0, 142.5, 141.5, 139.1, 132.4, 129.1, 124.1, 123.7, 119.7, 119.5, 109.2, 103.3, 101.6, 93.7, 80.5, 58.2, 40.4, 37.2; MS (ES+) m/z 422.1 (M + 1) 〇 Example 11.2 14(2-Offluent-4-yl-l,3-p-axazol-5-yl)methyl]spiro[吱,[2,3-f][i,3]benzene Synthesis of dioxolene-7,3|-吲哚]-2,(1,11)-one

According to the procedure as described in Example 11.1, and the insignificant changes were made, the use of chloroform, Lin substituted diamine to obtain morphine _4_yl 4,3^serazole _5_yl)methyl] Snail [Miso-[2,3-f][l,3]benzodioxolene-7,3,_吲哚]-2,(1Ή)- 143924-sp-20091127-4 •685· 201020257 ketone (71%) as a colorless solid: mp. 97-99 ° C; WNMR </ RTI> </ RTI> </ RTI> δ 7.28 (dd, J = 7.5, 7.5 Hz, 1H), 7.23 (s, 1H), 7.16 (d, J = 7.5 Hz , 1H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.97 (d, J = 7.5 Hz, 1H), 6.51 (s, 1H), 6.11 (s, 1H), 5.91-5.84 (m, 2H), 5.05 (d, J = 15.6 Hz, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.85 (d, J = 15.6 Hz, 1H), 4.64 (d, J = 9.0 Hz, 1H) , 3.78 (t, J = 4.8 Hz, 4H), 3.43 (t, J = 4.8 Hz, 4H) ; 13C NMR (75 MHz, CDC13) (5 177.3, 172.3, 156.1, 149.1, 142.5, 141.4, 138.6, 132.4 , 129.1, 124.2, 123.8, 120.9, 119.4, 109.1, 103.3, 101.7, 93.8, 80.5, 66.2, 58.2, 48.6, 37.0; MS (ES+) m/z 464.1 (M + 1). Example 11.3 Γ-[(2 -hexahydropyridin-1-yl-1,3-, pizozol-5-yl)methyl]spiro[吱,[2,3-f][l,3]benzodioxolene- Synthesis of 7,3'-吲哚]-2'(1Ή)-ketone

Following the procedure as described in Example 11.1, and carrying out irrelevant changes, hexylamine was used to replace the dimethylamine to obtain 1'-[(2-hexahydropyridin-1-yl-1,3-pyrazole-5). -yl)methyl]spiro[furo[2,3-phan[1,3]benzodioxol-7,3'-throindole]-2'(1Ή)-one (98%), Colorless solid: mp 195-197 ° C; 1H NMR (300 MHz, CDC 13) δ 12 Ί (ddd, J = 7.5, 7.5, 0.9 Hz, 1H), 7.17 (s, 1H), 7.16 (d, J = 7.5 Hz, 1H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.98 (d, J = 7.5 Hz, 1H), 6.51 (s, 1H), 6.14 (s, 1H), 5.90-5.84 (m , 2H), 5.04 (d, J = 15.6 Hz, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.85 (d, J = 15.6 Hz, 1H), 4.65 (d, J = 9.0 Hz, 1H ), 3.46-3.36 (m, 4H), 1.70-1.57 (m, 6H); 13 C NMR (75 MHz, CDC13) δ 177.2, 172.3, 156.1, 149.0, 142.5, 141.5, 138.6, 132.4, 129.1, 124.1, 123.7, 119.5, 119.4, 109.2, 143924-sp-20091127-4 -686- 201020257 103.3, 101.6, 93.7, 80.5, 58.2, 49.8, 37.1, 25.1, 24.1; MS (ES+) m/z 462.1 (Μ + 1) . Example 11.4 Γ-[(2-Methoxy-1,3-disazo-5-yl)methyl] succinf[2,3-f][l,3]benzodioxolene Synthesis of -7,3'-La 哚]-2·(1Ή)-ketone

© Γ-[(2-曱-oxy-1,3-oxazol-5-yl)indolyl was obtained by replacing the diamine with sodium methoxide according to the procedure as described in Example 11.1 and carrying out irrelevant changes. Spirulina [furo[2,3-f][l,3] stupid and dioxolene-7,3·-吲哚]-2'(1Ή)-one (19%) as a colorless solid: Mp 164-166°C; iHNMRGOOMHz 'CDCls) δ 7.28 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.20-7.13 (m, 2H), 7.06 (dd, J = 7.5, 7.5 Hz, 1H) , 6.95 (d, J = 8.1 Hz, 1H), 6.51 (s, 1H), 6.11 (s, 1H), 5.90-5.84 (m, 2H), 5.05 (d, J = 15.6 Hz, 1H), 4.92 ( d, J = 9.0 Hz, 1H), 4.85 (d, J = 15.6 Hz, 1H), 4.65 (d, J = 9.0 Hz, 1H), 4.03 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.2, 175.7, 156.1, 149.1, 142.5, 141.3, 136.2, 132.4, 129.1, 124.7, 124.3, 123.9, 119.3, 108.9, 103.2, 101.7, 93.8, 80.5, 58.4, 58.2, 37.2; MS (ES+) m/z 409.1 (M+ 1). Example 11.5 Γ-(hexahydropyridin-4-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3'-oxime Synthesis of -2'(1Ή)-ketone 143924-sp-20091127-4 &gt;687- 201020257

4-[(2'-keto-5,6-dihydrospiro[benzo[127:5,4-7,]difuran-3,34哚]_Γ(2Ή)-yl)indolyl] A solution of the hexahydropyridine carboxylic acid tri-butyl ester (94 g, 198 mmol) and trifluoroacetic acid (2 mL) in dioxane (1 mL) was stirred at ambient temperature for 1.5 h. The reaction was made up with 1% aqueous sodium hydroxide (30 mL) and extracted with di-methane (3×25 mL). The combined organic solution was dried over sodium sulfate, filtered, and concentrated under reduced pressure to give </RTI> <RTIgt; </RTI> (hexahydropyridin-4-ylmethyl)-5,6-dihydrospiro[benzo[i,2- b: 5,4-b,]difuran-3,3,-吲哚]-2'(1Ή)-_ (0.73 g '98%) as colorless solid: 1H NMR (300 MHz, CDC13) δ 7.30 (dd, J = 7.8, 7.5 Hz, 1H), 7.16 (d, J = 6.9 Hz, 1H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H) , 6.45 (s, 1H), 6.41 (s, 1H), 4.91 (d, J = 8.9 Hz, 1H), 4.66 (d, J = 8.9 Hz, 1H), 4.54 (t, J = 8.6 Hz, 2H) , 3.71 (dd, J = 13.9, 7.5 Hz, 1H), 3.57 (dd, J = 13.9, 7.1 Hz, 1H), 3.21-3.11 (m, 2H), 2.99 (td, J = 8.7, 2.7 Hz, 2H ), 2.74 (br s, 1H), 2.67-2.56 (m, 2H), 2.08-1.94 (m, 1H), 1.77-1.66 (m, 2H), 1.44-1.30 (m, 2H) ° Example 11.6 1' -{[1-(1-mercaptoethyl)hexafluoropypto-4-yl]hydrazino}-5,6-dihydrospiro[benzo

143924-sp.20091127-4 -688- 201020257 i, (hexahydropyridin-4-ylmethyl)-5,6-dihydrospiro, which is sealed in a round bottom flask filled with a plug. Stupid [i,2_b : 5,4-b'] II bite -3,3Ί 嗓]· 2'(1Ή)-ketone (0.29 g, 0.77 mmol), acetone (〇1〇 ml, i 4 a solution of sodium cyanoborohydride (0.10 g, 1.51 mmol) and acetic acid (6 drops) in methanol (4 mL). Dilute with a saturated aqueous solution of sodium hydrogencarbonate (30 mL), and then extract with di-methane (3 </ </ RTI> 25 </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> The organic solution was dried over sodium sulfate, filtered, and evaporated under reduced pressure. Purification, using dioxin/methanol® (14:1) to obtain Γ-{[1-(1-methylethyl)hexahydropyridinyl-4-yl]methyl b 56 dihydrospiro[benzo[ l,2-b: 5,47']difuran-3,3'-indole]-2,(1Ή)-one (0.21 g, 64%), as a colorless foam: 1H NMR (300 MHz, CD3 OD) (5 7.33 (ddd, J = 7.8, 7.5, 0.9 Hz, 1H), 7.14-7.05 (m, 3H), 6.44 (s, 1H), 6.32 (s, 1H), 4.81 (d, J = 9.2 Hz, 1H), 4.65 ( d, J = 9.2 Hz, 1H), 4.99 (t, J = 8.7 Hz, 2H), 3.74 (dd, J = 14.0, 7.2 Hz, 1H), 3.65 (dd, J = 14.0, 7.1 Hz, 1H), 3.02-2.91 (m, 4H), 2.77 (seven peaks, J = 6.6 Hz, 1H), 2.30-2.18 (m, 2H), 2.00-1.84 (m, 1H), 1.81-1.71 (m, 2H), © 1.50-1.34 (m, 2H), 1.08 (d, J = 6.6 Hz, 6H); 13 C NMR (75 MHz, CD3 OD) δ 180.3, 163.2, 162.9, 144.1, 134.1, 123.0, 124.8, 124.6, 121.6, 121.4, 120.0, 110.5, 93.7, 81.7, 73.5, 59.2, 56.2, 49.5, 49.4, 46.6, 36.0, 30.7 (2C), 29.9, 1.8.3, 18.3 ; MS (ES+) m/z 419.2 (M + 1) . Example 11.7 l'-{[1-(1-Mercaptoethyl)hexahydropyridin-4-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b: 5,4- Synthesis of b']difuran-3,3W丨哚]-2·(1Ή)-ketohydrochloride 143924-sp-20091127-4 -689- 201020257

Γ-{[1-(1-methylethyl)hexahydropyridine_4_yl]methyl b 5,6-dihydrospiro[benzo-[1'2-b : 5,4-b' Difuran-3,3'-indole]-2'(1Ή)-one (0.21 g, 0.49 mmol) and 4 Μ hydrochloric acid (0.50 mL, 2.0 mmol) in 1,4-dioxane The solution in decyl alcohol (丄 5 mL) was stirred at ambient temperature for 30 minutes. Remove the solution under reduced pressure

The residue was suspended in ethyl acetate/hexane, and the formed precipitate was collected by filtration. The precipitate was dried to give 1,_{[1_(1-methylethyl)hexahydroacridin-4-yl]methyl}-5,6-dihydrospiro[benzo[l,2-b : 5,4-b,]difuran-3,3Ί noise]-2'(1Ή)-ketohydrochloride (0.17 g, 76%) 'as colorless powder: dazzle point i67 ° C (decomposition) 1H NMR (300 MHz, CD3 OD) (5 7.36 (ddd, J = 7.8, 7.2, 1.2)

Hz, 1H), 7.19-7.08 (m, 3H), 6.48 (s, 1H), 6.33 (s, 1H), 4.83 (d, J = 9.3 Hz, 1H), 4.67 (d, J = 9.3 Hz, 1H ), 4.51 (t, J = 8.6 Hz, 2H), 3.80 (dd, J = 14.3, 7.5 Hz, 1H), 3.73 (dd, J = 14.3, 7.1 Hz, 1H), 3.54-3.42 (m, 3H) , 3.07-2.96 (m, 4H), 2.31-2.16 (m, 1H), 2.09-1.98 (m, 2H), 1.76-1.60 (m, 2H), 1.35 (d, J = 6.6 〇Hz, 6H); 13 C NMR (75 MHz, CD3 OD) δ 180.4, 163.3, 162.9, 143.8, 134.0, 130.1, 124.9, 124.8, 121.5 (2C), 120.1, 110.4, 93.7, 81.8, 73.5, 59.7, 59.3, 49.5, 45.8, 34.1, 29.9, 28.7, 28.67, 17.0; MS (ES+) m/z 419.3 (M + 1); Calculated for C26H3 〇N203 · HC1 · 2H20: C, 63.60; H, 7.18; N, 5.71; Value: C, 63.80; H, 6.83; N, 5.67. Example 11.8 Γ-[(1-ethylhexafluoropyridin-4-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']

143924-sp-20091irM -690-

(S 201020257 One bite ° South-3,3·-ρ5 Bu Duo)-2·(1Ή)-_The synthesis of 1·-(hexahydropyridinyl group fyl)_5,6-dihydrospiro[benzo [U b : 5 4 b-furfuran-3'3,-+ flower]-2, (1'Η)__ (〇3γg, 〇99mmol), acetaldehyde liter, I. 4 millimol And a mixture of sodium triethoxysulfonate hydride (1.32 g, 151 mmol) in U-diethane (4 mL) was stirred at ambient temperature for 175 min. The orange reaction mixture was diluted with saturated aqueous NaHCO3 (3 mL). The organic solution was dried over sodium sulfate, filtered, and evaporated. Purification by flash column chromatography using dichloromethane/methanol (19:1) to give 14 (1-ethylhexahydropyridinyl)methyl]-5,6-dihydrospiro[benzo[ 1,2-b: 5,4-b']dipyran-3,3·-bend]-2,(1Ή)-_ (0.32 g '80%), yellow foam: 1 η NMR (3〇〇MHz, CDC13) δ 7.29 (ddd, J = 7.8, 7.8, 1.4 Hz, 1H), 7.15 (dd, J = 7.5, 0.9 Hz, 1H), 7.04 10 division, J = 7.5, 7.5, 0.8 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H), 6.45 (s, m), 6·41 1H), 4.90 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz , 1H), 4.53 (t, J = 8.6 Hz, 2H), 3.73 (dd, J = 14.0, 7.4 Hz, 1H), 3.60 (dd, J = 14.0, 7.1 Hz, 1H), 3.10-2.95 (m, 4H), 2.52 (q, J = 7.1 Hz, 2H), 2.14-1.87 (m, 3H), 1.83-1.72 (m, 2H), 1.67-1.52 (m, 2H), 1.15 (t, J = 7.1 Hz , 3H) ; 13C NMR (75 MHz, CDC13) δ 178.2, 161.9, 161.5, 143.0, 132.9, 128.9, 124.1, 123.4, 120.3, 120.0, 118.9, 108.8, 93.4, 80.9, 72.5, 57.8, 52.6, 45.8, 34.5 , 29.6, 29.5, 29.2, II. 7; MS (ES+)m/z 405.2 (M + l) » Example 11.9 143924-sp-20091127^ -691- 201020257

Γ-[(1-ethylhexahydropyridin-4-yl)methyl]·5,6-dihydrospiro[benzo[12_b : 5 4 b,] a pfu _3,3'-〇5卜多]: Synthesis of 2'(1Ή)-ketohydrochloride Γ-[(1-ethylhexahydropyridin-4-yl)indolyl]_5,6-dihydrospiro[benzo[12_b: 5 , 4 seven '] two blowing Ming-3,3'-'1 嗓]-2' (1'11)-ketone (〇.17g '〇.41 millimolar) and hydrogenated hydrogen (4.0M, in A solution of '0.40 ml, ι. 6 mmoles in 1,4-dioxane in decyl alcohol (1 mL) was stirred at ambient temperature for 35 minutes. The dissolved beta agent was removed under reduced pressure, and the residue was suspended in ethyl acetate /hexane, and then collected, and washed with hexane. The precipitate was dried to give 1 L [(1-ethylhexahydroindole-4-yl)methyl]-5,6-azaspiro[本,[l,2-b: 5,4-b' ] 2 p lost -3,3: »5丨哚]-2'(m)-keto hydrochloride (0.18 g, 100%), as an off-white powder: melting point 135 ° C (decomposition) (hexane) ;1H NMR (300 MHz, CD3 OD) (5 7.36 (dd, J = 6.9, 6.6

Hz, 1H), 7.20-7.07 (m, 3H), 6.49 (s, 1H), 6.32 (s, 1H), 4.83 (d, J = 9.2 Hz, 1H), 4.67 (d, J = 9.2 Hz, 1H ), 4.50 (t, J = 8.3 Hz, 2H), 3.84-3.68 (m, 2H), 3.65-3.54 (m, 2H), 3.21-3.10 (m, 2H), 3.02-2.87 (m, 4H), 2.31-2.16 (m, 1H), 2.08-1.95 (m, 2H), 1.76-1.58 (m, 2H), 1.35 (t, J = 6.2 Hz, 3H); 13C NMR (75 MHz, CD3OD) δ 180.4, 163.2, 162.9, 143.8, 133.9, 130.1, 124.9, 124.8, 121.5 (2C), 120.1, 110.5, 93.7, 81.8, 73.5, 59.2, 53.4, 53.0, 45.9, 34.0, 29.9, 28.7 (2C), 9.7; MS ( ES+) m/z 405.2 (M + 1). Example 11.10 Γ-[(1-Methylhexahydropyridin-4-yl)methyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3 , 3Wh fruit]-2' (1Ή)-_ synthesis 143924-sp-20091127-4 • 692- (S) 201020257

Γ-(hexahydropyridin-4-ylmethyl&gt;5,6-dihydrospiro[benzo[u_b:5,4_bi]difuryl-3,3W丨嗓]-2, (1,H&gt; (0.354 g, _mole), formaldehyde solution (37% in water, 0.80 ml, 10.6 mmol) and citric acid (8 ml, 212 mmol) in water (2 ml) The mixture was stirred for 145 hrs. EtOAc (EtOAc m. Concentration under reduced pressure. Purification by flash column chromatography using methanol / di-methane / ammonium hydroxide (32:1:0.17, to 19:1:0.2) to obtain ι, _[(ι_ Mercaptohexahydropyridine_4_yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]dioxan-3,3^5b]]- 2·(1Ή)-ketone (0.18 g '48%) as colorless solid: mp 155-158°C (hexanes); WNMR (300 MHz, CDC13) δ 7.30 (dd, J = 7.8, 7.5 Hz, 1H ), 7.16 (d, J = 6.9 Hz, 1H), 7.04 (dd, J = 7.5, 7.2 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.45 (s, 1H), 6.41 (s , φ 1H), 4.91 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.54 (t, J = 8.6 Hz, 2H), 3.72 (dd, J = 14.0, 7.4 Hz, 1H), 3.58 (dd, J = 14.0, 6.9 Hz, 1H), 2.99 (td, J = 8.3, 1.2 Hz, 2H), 2.91-2.82 (m, 2H), 2.27 (s, 3H), 1.97-1.80 (m, 3H), 1.75-1.65 (m, 2H), 1.53-1.38 (m, 2H) ; 13C NMR (75 MHz, CDC13) &lt;5 178.1, 161.9, 161.5, 143.0, 133.0, 128.8, 124.1, 123.3, 120.3, 120.0, 118.9, 108.7.93.3.80.9.72.5.57.7.55.3.46.5. For the analysis of C24H26N203: C, 73.82; H, 6.71; N, 7.17; found: C, 73.46; H, H,,,,,,,,,,,,,,,,,,,,, 7.10; N, 7.22. Example 11.11 143924-sp-20091127-4 -693- 201020257 l'-[(2S)-tetraazaindole-2-ylindenyl]_5,6-dihydrospiro [stupid [speak: 5,4 b, Synthesis of two biting _3'3'-吲哚]_2, (γη)-鲖

According to the procedure described in Example 11.5, and with irrelevant changes, use (2S)-2-[(2'-mercapto-5,6-dihydrospiro[benzo[i,2:7:5,4) -b']diterpenoid-3,3,-啕嗓]-1'(2Ή)-yl)indolyl]tetrahydropyrrole_ι_carboxylic acid third-butyl ester replacement 4_[(2,-ketone) Benzyl-5,6-dihydrospiro[benzo[l,2-b:5,47']di-n-but-3,3,-蚓哚]-1,(2Ή)-yl)indenyl] Hydrogen pyridine-1-carboxylic acid tert-butyl ester, replacing dihalogen methane with tetrahydrofuran to obtain l'-[(2S)-tetrahydropyridin-2-ylindenyl]-5,6-dihydrospiro[benzene And [i,2-b: 5,4-b,]difuran-3,3'-indole]-2'(anthracene)-one (89%) 'as pale yellow solid: mp. 83-86. (: (hexane); 1H NMR (300 MHz, CDC13) ( diastereomer) &lt;5 7.29 (dd, J = 7.8, 7.5 Hz, 1H), 7.16 (d, J = 7.5 Hz, 1H ), 7.07-6.99 (m, 2H), 6.52, 6.46 (s, 1H), 6.40 (s, 1H), 4.95, 4.91 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.53 (t, J = 8.7 Hz, 2H), 3.91-3.71 (m, 2H), 3.69-3.60 (m, 1H), 3.14-2.90 (m, 5H), 1.98-1.70 (m, 3H) , 1.66-1.51 (m, 1H); MS (ES+) m/z 363.1 (M + 1). Example 11.12 3-[(2'-keto-5,6-dihydrospiro[benzo[l,2 -b: Synthesis of 5,4-b']difuran-3,3'-吲哚]-Γ(2Ή)-yl)indolyl]benzoic acid

143924-sp-20091127-4 -694· 201020257 in 3-[(2,-keto-5,6-dihydrospiro[benzon,2_b:5,4_b,]difuran_3,3,_10 Add methyl hydroxide to a solution of methyl 4-(H)-yl)methyl]benzoate (280 g, 65 mmol) in tetrahydrofuran (30 mL) and water (10 mL) Monohydrate (0.82 g, 19 mmol). The reaction mixture was stirred at ambient temperature for π hours. Most of the tetrahydrofuran was removed in vacuo and the resulting solution was washed with diethyl ether (2.times.50 mL). The water was made acidic with respect to the leanness by adding 1 M hydrochloric acid and extracted with ethyl acetate (3 X 5 mL). The combined organic solution was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was triturated with diethyl ether (50 mL). EtOAcjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj 6-Dihydrospiro[benzo[l,2-b:5,4-b']dioxin-3,3.-4丨嗦]-Γ(2'Η)-yl)indenyl]benzoquinone Acid (2.20 g, 81%), colorless solid: melting point &gt;〇(water); 1 η NMR (300 MHz, DMSO-d6) δ 13.06 (br s, 1H), 7.89-7.82 (m, 2H), 7.66 (d, J = 7.6 Hz, 1H), 7.55-7.47 ( m, 1H), 7.29-7.16 (m, 2H), 7.07-6.96 (m, 2H), 6.49 (s, 1H), 6.42 (s, 1H), 5.17-4.72 (m, 4H), 4.55-4.45 ( m, 2H), 3.06-2.88 ((m, 2H) ; 13C NMR (75 MHz, DMSO-de) &lt;5 177.2, 167.1, 161.2, 160.7, 142.0, 136.9, 132.2, 131.8, 131.2, 129.1, 128.8, 128.4, 127.3, 123.8, 123.2, 120.5.120.0. 118.9, 109.3, 92.5, 79.7, 72.1, 57.0, 42.5; MS (ES+) m/z 414.0 (M+l). Example 11.13 Γ-{4-[5-(Trifluoromethyl)-l,2,4-oxadiazol-3-yl]-p-butyl 5,6-dihydrospiro[benzo[l,2-b : Synthesis of 5,4-b']difuran-3,3'-indole]-2'(1Ή)-one 143924-sp-20091127-4 -695- 201020257

Μ-Hydroxy-4-[(2'-keto-5,6-dihydrospiro[benzo[1,2:7:5,4-b,] two-scented-3,3'-蚓嗓] -1'(2Ή)-yl)indolyl] benzoquinone imine amide (〇4 g, 0.94 mmol) and trifluoroacetic anhydride (0.4 ml) in pyridine (2 mL) 'At 170 ° C' in a microwave reactor for 30 minutes. The solution was concentrated to dryness in vacuo and purified by flash chromatography eluting with EtOAc EtOAc EtOAc EtOAc EtOAc Base)-1,2,4^diazol-3-yl]-yl}-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxin-3 , 3'-»»引嗓]-2'(1Ή)-ketone (0.34 g, 71%) as colorless solid: mp 178-179 ° C; 4 NMR (300 MHz, CDC13) δ 8.09 (d, J = 8.2 Hz, 2H), 7.49 (d, J = 8.2 Hz, 2H), 7.24-7.16 (m, 2H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.76 (d, J = 7.7 Hz , 1H), 6.48 (s, 1H), 6.42 (s, 1H), 5.15 (d, J = 15.9 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.90 (d, J = 15.9 Hz , 1H), 4.71 (d, J = 9.0 Hz, 1H), 4.54 (t, J = 8.62 Hz, _ 2H), 3.07-2.93 (m, 2H); 1 3 C NMR (75 MHz, CDC13) &lt; 5 194.7, 178.0, 168.8, 162.0, 161.4, 141.8, 140.4, 132.7, 128.8, 128.3, 128.1, 124.5, 124.1, 123.7, 120.0, 118.8, 116.0 (q, J = 273.8 Hz), 109.1, 93.4, 80.7, 72.4 , 57.8, 43.9, 29.1; MS (ES+) m/z 506.0 (M + l). Example 11.14 Γ-[4-(5-Mercapto-1,2,4-oxadiazol-3-yl)benzyl]-5,6-dihydrospiro[benzo[l,2-b: 5, Synthesis of 4-b']difuran-3,3'-throindolin]-2'(1Ή)-one 143924-sp-20091127-4 -696· (S) .0 201020257

According to the procedure as described in Example 11.13, and irrelevant changes were made, trifluoroacetic anhydride was replaced with chlorohydrazine to obtain Γ_[4(5-methylindole-3-yl)-yl]-5. 6-Dihydrospiro [stupid [u_b: 5 4-7,]difuran_3,3,,哚]_ 2'(1Ή)-_ (82%) ' is a colorless solid: melting point 185_186〇c; ihnmr ( 3〇〇MHz, CDC13) δ 8.03 (d, J = 8.1 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.25-7.14 (m, 2H), 7.02 (dd, J = 7.5, 7.5 Hz, 1H), 6.77 (d, J = 8.2 Hz, 1H), 6.47 (s, 1H), 6.42 (s, 1H), 5.13 (d, J = 15.8 Hz, 1H), 4.98 (d, J = 9.0 Hz, 1H), 4.86 (d, J = 15.8 Hz, 1H), 4.71 (d, J = 9.0 Hz, 1H), 4.53 (t, J = 8.6 Hz, 2H), 3.10-2.89 (m, 2H), 2.63 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 176.7, 168.0, 161.9, ❹ 161.4, 141.9, 139.0, 132.7, 128.8, 127.9 (2C), 126.4, 124.0, 123.6, 120.1, 120.0, 118.8, 109.2, 93.3, 80.6, 72.4, 57.8, 43.9, 29.1, 12.4; MS (ES+) m/z 451.9 (M + 1). Example 11.15 Γ-[(5-ρ-pyridin-4-ylfuran-2-yl)methyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b]

N 143924-SD-20091127-4 -697- 201020257 will l'-[(5-bromobutan-2-yl)methyl]-5,6-dihydrospiro [stupid [i,2-b: 5,4-b,] difuran-3,3,-吲哚]-2,(1Ή)-one (0.22 g '0.5 mmol), pyridinyl dihydroxyborane (0.09 g ' 0'75 Millol), bismuth (triphenylphosphine) palladium (〇·〇6 g, 〇.〇5 mmol) and sodium carbonate (1 ml, 2 Μ aqueous solution, 2.0 mmol) in ν,Ν-dimethyl The mixture in formamide (4 ml) was heated in a microwave reactor at 15 ° C for 15 minutes. The reaction mixture was subjected to column chromatography using ethyl acetate/hexane (1:1) to give 1'-[(5-pyridin-4-ylfuran-2-yl)indolyl]-5,6- Dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3'-啕哚]-2'(ΓΗ)-嗣(0.15 g, 66%), as a colorless solid :1H NMR (300 MHz, CDC13) &lt;5 8_55 (s, 2Η), 7.52-7.00 (m, 6H), 6.83 (d, J = 3.4 Hz, 1H), 6.48 (d, J = 3.4 Hz, 1H ), 6.40 (s, 1H), 6.38 (s, 1H), 5.00 (ABq, 2H), 4.81 (ABq, 2H), 4.52-4.44 (m, 2H), 2.87 (t, J = 8.6 Hz, 2H) 13C NMR (75 MHz, CDC13) &lt;5 177.5, 161.8, 161.2, 151.0, 150.8, 149.7, 141.6, 137.3, 132.6, 128.7, 124.0, 123.7, 120.1, 119.9, 118.8, 117.7, 111.2, 110.0, 108.9, 93.2, 80.4, 72.3, 57.6, 37.2, 28.9; MS (ES+) m/z 436.8 (M+l). Example 11.16 Γ-(4-Pyridin-3-ylindenyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3'-吲哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 11.15, and with irrelevant changes, 143924-SP-20091127-4 -698-201020257 replaced pyridin-4-yldihydroxyborane with pyridin-3-yldihydroxyborane, and Use of Γ-(4-bromobenzyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran-3,3·-吲哚]-2' ( 1Ή)-ketone replacement l'-[(5-bromofuran-2-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran -3,3'-吲哚]-2,(1Ή)-one, obtaining l'-(4-pyridin-3-yl-yl)-5,6-dihydrospiro[benzo[l,2-b : 5,4-b']difuran-3,3'-indole]-2'(1Ή)-one (42%) as colorless solid: iHNMR (300MHz, CDC13) 5 8.73-8.69 (m,1Η ), 8.49-8.44 (m, 1H), 7.95-7.88 (m, 1H), 7.59-6.79 (m, 9H), 6.45 (s, 1H), 6.35 (s, 1H), 5.11-5.01 (m, 1H) ), 5.11-4.81 (m, 3H), 4.67 (dd, J = 9.1, 1.42 Hz, 1H), ® 4.48 (t, J = 8.6 Hz, 2H), 3.05-2.86 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 181.4, 164.7, 164.2, 150.4, 150.0, 144.8, 139.7, 139.6, 138.9, 138.3, 135.4, 131.8, 131.1, 130.5, 127.1, 126.8, 126.7, 123.0, 121.8, 112.3, 96.0, 83.4 , 75.3, 60.8, 46.6, 31.8 ; MS (ES+) m/z 446.8 (M + 1). Example 11.17 Fluorobiphenyl-4-yl)indolyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3W丨哚]-2 ·(1·Η)-胴 Synthesis

Follow the procedure as described in Example 11.15 and perform irrelevant changes using 2-fluorophenyldihydroxyborane to displace pyridine-4-yldihydroxyboron and use 1·-(4-bromobenzyl) -5,6-dihydrospiro [stupid [12 VII · 5 4_b,] difuran _33, _, 丨嗓 丨嗓] -2 · (1Ή)-嗣 replacement l'-[(5-bromofuran _2 yl)methyl]5 6 dihydrospiro [benzoxanthene 143924-sp-20091127-4 201020257 [l,2-b: 5,4-b']difuran-3,3'-啕哚]- 2·(1Ή)-ketone, obtained Γ-[(2·-fluorobiphenyl-4-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4- b']difuran-3,3'-indole]-2·(1Ή)-one (34%), colorless solid: 111 paintings 11 (30〇]\«^,00(:13)(5 8 ;72- 7.91 (m, 12H), 7.61 (s, 1H), 7.54 (s, 1H), 6.11 (ABq, 2H), 5.97 (ABq, 2H), 5.64 (t, J = 8.6 Hz, 2H), 4.20-4.01 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 177.9, 161.8, 161.3, 158.0, 142.1, 135.3 (2C), 135.2, 132.8, 130.6 (2C), 129.5, 129.4, 129.2, 129.1 , 128.7, 128.4, 128.3, 127.5, 124.4 (2C), 123.9, 123.4, 120.2, 119.9, 118.9, 116.3, 116.0, 109.3, 93.2, 80.6, 72.4, 57.7, 43.9, 29.0. 11.18 Γ-{2-[5-(Trifluoromethyl)-i, 2,4-dioxa-3-yl]ethyl} sulphate [2,3-f][i,3] Synthesis of benzodioxol-7,3'-吲嗓]-2'(1Ή)-one

Ν-Hydroxy-3-(2'-keto-6Η-spiro[benzofuro[6,5_d][13]dioxosylylene-7'3'-dihydroindole]-indole a propanolamide (〇·5〇g, 丄*mole) and diisopropylamine (0.3 ml, 2.0 mmol) in a stirred solution of di-methane (2 mL) Add trifluoromethyl acetic anhydride (0.3 ml, 2.0 mmol). The solution was stirred at ambient temperature for 1 hour, then subjected to liquid separation with saturated aqueous ammonia (10 ml) in water, and the aqueous layer was extracted with a second gas (2 mL). The combined organic solution was dried over sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by flash chromatography using 143924-sp-20091127-4

-700- 201020257 Ethyl acetate in hexane (15% to 50% gradient) to give Γ-{2-[5-(trifluoromethyl hydrazine, 2,4-oxadiazol-3-yl) Ethyl} snail [吱,[2,3-f][l,3] stupid and bismuthene-7,3'-啕哚]-2'(1Ή)-one (0.20 g, 33%) ), as a colorless solid: mp 45-48 ° C; 1H NMR (300 MHz, CDC13) δ Ί.2Ί-Ί.20 (m, 1H), 7.14 (d, J = 7.1 Hz, 1H), 7.03 (dd , J = 7.5, 7.5 Hz, 1H), 6.76 (d, J = 7.8 Hz, 1H), 6.48 (s, 1H), 6.23 (s, 1H), 5.87-5.83 (m, 2H), 4.74 (ABq, 2H), 4.27-4.05 (m, 2H), 3.28 (td, J = 6.4.1.5 Hz, 2H); 13 C NMR (75 MHz, CDC13) δ 111.6, 168.8, 166.0 (q, J = 44.5 Hz), 155.9, 148.9, 142.4, 141.4, 132.4, 128.8, 124.3, 123.6, 119.1, 115.8 ® (q, J = 273.9 Hz), 107.8, 103.3, 101.5, 93.5, 80.5, 5B.1, 37.8, 24.2; MS (ES+ m/z 446.1 (M + 1). Example 11.19 4'-Gasyl-1'-{[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl} Synthesis of snail [吱,[2,3〇[1,3]benzodioxanthene-7,3W丨哚]-2·(1Ή)-one

2-(4'-Chloro-2,-oxo-[N-[2,3&lt;][1,3]benzodioxolene-7,3,_W嗓]-1' ( 2Ή)-yl)_Ν·_ via acetamimidamide (〇·39 g, j 〇 millimol) with monoisopropylamine (0.20 ml, 1.5 mmol) in dichloromethane (2 〇 Trifluoromethane acetic anhydride (〇 21 ml, 15 mmol) was added to the stirred solution in ML). The solution was stirred at ambient temperature for 2 h then concentrated in vacuo andEtOAcEtOAcEtOAc The ethyl acetate solution was washed with a saturated aqueous solution of ammonium sulfate (2×25 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to dry. Purification of the residue by flash chromatography

143924-sp-20091127-4 -701 - 201020257 Ethyl acetate in hexane (15% to 50% gradient), giving ι, -{2-[5-(trifluoromethyl)-1,2, 4-oxadiazol-3-yl]ethyl}spiro[吱,[2,3-f][l,3]benzodioxolene-7,3·-吲哚]-2'( 1 Ή)-ketone (0.13 g, 29%) as colorless solid: mp 138-140 ° C; 1H NMR (300 MHz, DMSO-d6) δ 7.34 (dd, J = 8.0, 8.0 Hz, 1H), 7.15 ( d, J = 7.9 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 6.67 (s, 1H), 6.27 (s, 1H), 5.30 (ABq, 2H), 4.81 (ABq, 2H); 13C NMR (75 MHz, DMSO-d6) δ 176.8, 167.6, 165.8 (q, J = 106.3 Hz), 156.6, 149.1, 143,7, 142.0, 131.0, 130.3, 128.4, 124.3, 117.1, 116.0 (q,J = 273.2 Hz), 109.0, 103.2, 102.0, 93.4, 77.3, 58.4, 36.1; MS (ES+) m/z 466.0 (M + 1). · Example 11.20 4'-Chloro-indole-[(5·cyclopropyl-i,2,4-oxadiazol-3-yl)indolyl] snail [吱,[2,3-f][l ,3] Synthesis of benzodioxanthene _7,3,_吲哚]_2,(1Ή)__

N~〇 will be 2-(4'-chloro-2,-oxaspiro[吱-benzobenzodioxene_7,3,_10 (five)嗓Η'(2Ή)-yl)_ν'-[( The stirred solution of cyclopropylcarbonyl)oxy]acetimimine indoleamine (24 g, 0.52 mmol) in pyridine hexanes was heated in a microwave reactor for 30 minutes at 17 °C. The solution was concentrated to dryness on a vacuum card, and purified by flash chromatography, using ethyl acetate (15% to 5% by weight gradient) in hexanes to give 4'-gas-based Γ[[5_ring Propyl-u,4_oxadiazole_3yl)methyl]spiro[吱,[2,3-f][l'3]benzodioxanthene_7 3,_吲哚]_2 , (1Ή)-ketone (〇36g, 16%), as colorless solid: mp 18 〇 182 〇c; lHNMR (3〇〇MHz CDCl3) δ 7.19 (dd, J = 8.1, 8.1 Hz, 1H), 6.99 (d, J = 8.4 Hz, 1H), 6.77 (d, J = 7.8 Hz, 143924-sp-20091127-4 • 702·

201020257 1H), 6.46 (s, 1H), 6.28 (s, 1H), 5.86 (d, J = 1.2 Hz, 1H), 5.04 (ABq, 2H), 4.94 (ABq, 2H), 2.20-2.10 (m, 1H), 1.26-1.12 (m, 4H); 13C NMR (75 MHz, CDC13) δ 182.9, 177.0, 165.4, 156.8, 149.2, 143.0, 142.1, 131.6, 130.0, 128.4, 124.6, 116.5, 107.4, 103.0, 101.5 , 93.2, 58.7, 36.1, 10.57, 10.53, 7.8; MS (ES+) m/z 438.1 (M + 1). Example 11.21 4'-Chloro-indole-{1-[5-(difluoroindolyl)-l,2,4-oxadiazol-3-yl]ethyl} snail [吱. Synthesis of Nanhe [2,3-ί][1,3]benzodioxanthene-7,3'-吲哚]-2·(1Ή)-one

According to the procedure as described in Example 11.19, and irrelevant changes were made, the trifluoromethyl acetic anhydride was replaced with difluoromethyl acetic anhydride to obtain 4·-gas-Γ-{1-[5-(difluoro Mercapto)-1,2,4-oxadiazol-3-yl]ethyl}spiro[furo[2,3_phantom [1,3]benzodioxanthene-7,3W丨哚] -2Χ1Ή&gt; Ketone (35%) as a colorless solid: φ melting point 179-182°C; 1H NMR (300 MHz, CDC13) 5 7.25-7.17 (m,1Η), 7.03 (d, J = 8.1 Hz, 1H) , 6.76 (d, J = 7.6 Hz, 1H), 6.76 (t, J = 52.0 Hz, 1H), 6.47 (s, 1H), 6.24 (s, 1H), 5.86 (ABq, 2H), 5.15 (ABq, 2H), 4.94 (ABq, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.1, 170.6 (t, J = 30.2 Hz), 166.3, 156.8, 149.3, 142.6, 142.2, 131.9, 130.3, 128.2, 124.9, 116.1 , 107.1, 105.3 (t, J = 244.5 Hz), 102.9, 101.6, 93.3, 58.7, 35.8; MS (ES+) m/z 448.1 (M + 1). Example 11.22 1'-{[5-(Difluoromethyl)-l,2,4-oxadiazol-3-yl]indolyl} snail [吱,[2,3-f][l,3] Synthesis of benzodioxanthene-7,3·-吲哚]-2·(1Ή)-_ 143924-sp-20091127-4 -703· 201020257 •ο

Follow the procedure as described in Example 11.19, and perform irrelevant changes, replace the trifluoromethylacetate with difluoromethyl acetate, and use hydrazine, hydrazino-2-(2'-keto-6Η - snail [benzofuro[6,5 d][1,3]dioxosylylene-7,3,dihydrogen

啕哚]-Γ-yl) acetonitrile imine amide replacement 2_(4, chloro 2, oxa snail [bito-and-[2,3-f][l,3] benzodioxolan _7,3,_吲哚]_Γ(2Ή) group)_N, hydroxyacetammine indoleamine, obtaining 1'-{[5-(difluoromethyl H,2,4_oxadiazole_3_ Methyl]methyl snail [Miso-[2,3-f][l,3] benzodioxolane _7,3,_吲哚]_2, (ΓΗ)__ (67%), Colorless solid: mp 137-139 ° C; iHNMR pOO MHz 'CDClg) &lt;5 7.30-7.17 (m, 2H), 7.08 (dd, J = 7.5, 7.5 Hz, 1H), 6.85 (d, J = 7.8 Hz, 1H ), 6.76 (t, J = 52.0)

Hz, 1H), 6.50 (s, 1H), 6.26 (s, 1H), 6.85 (m# 2H), 5.16 (ABq, 2H), 4.82 (ABq, 2H) ; 13C NMR (75 MHz, CDC13) &lt; 5 177.4, 170.5, 166.5, 155.8, 149.0, 142.4, 140.8, 132.2, 129.1, 124.2, 124.1, 119.2, 108.6, 105.4 (t, J = 244.2 Hz), 103.3, 101.5, 93.6, 80.2, 58.2, 35.6; (ES+) m/z 414.1 (M + l). Example 11.23 Γ-[(5-Terve-butyl-l,2,4-g-oxadiazol-3-yl)methyl]spiro[吱,[2,3-f][l,3]benzo Synthesis of Dioxynene-7,3'-(4)哚]-2'(1Ή)-one

Ν'-Hydroxy-2-(2'-keto-6Η-spiro[benzofuro[6,5-d][l,3]dioxosole 143924-SP-20091127-4 -704-

(S 201020257 ene-7,3'-dihydro 4 fluorene]-fluorenyl) acetamimidamide (0.20 g, 0.57 mmol) with diisopropylamine (0.40 mL, 2.9 mmol) Trihydrocarbyl anhydride (0.2 ml, U mmol) was added to the stirred solution in di-methane (1 mL). The solution was stirred at ambient temperature for 2 hours and then concentrated in vacuo to give the intermediate 2-(2'-keto-6 Η- snail [stupid and suffol [6,5-d][l,3 Dioxin, -7,3'_monohydroindolyl]-indole-yl)-indole-(trimethylthioethyloxy)ethiniumamine. The crude residue was dissolved in pyridine (3 mL) EtOAc. (:, heating in a microwave reactor for 30 minutes. The solution was concentrated to dryness in vacuo, purified by flash chromatography, using ethyl acetate (15% to 50% gradient) in hexane to give 14 (5-Terti-butyl-1,2,4-indenyl-3-yl)methyl]spiro[吱]南和[2,3-f][l,3]benzodioxanthene Alkene-7,3'-indole]-2·(1Ή)-one (0.16 g, 67%), as colorless solid: mp 183-185 ° C; 4 NMR (300MHz, CDC13) 5 7.27-7.16 ( m, 2H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.85 (d, J = 7.5 Hz, 1H), 6.48 (s, 1H), 6.35 (s, 1H), 5.84 (d, J = 3.3 Hz, 2H), 5.05 (ABq, 2H), 4.83 (ABq, 2H), 1.39 (s, 9H) ; nC NMR (75 MHz, CDCl3) $ 1874, 1774, 1655, 1557, 1489, Q 142.4, 141.2, 132.4, 128.9, 123.9, 123.8, 119.7, 108.8, 103.5, 101.5, 93.5, 80.1, 58.3, 36,1,33.7, 28.3; MS (ES+) m/z 420.2 (M + 1). Example 11.24 14( 5-cyclopropyl-1,2,4-oxadiazoleyl)indenyl]spiro[,,[2,3_耶,3]benzodioxene-7,3,-吲哚]-2,(1Ή)-ketone synthesis

According to the procedure as described in Example 11.23, and the insignificant change was carried out, 143924-sp.20091127-4 -705- 201020257 replaced the tridecyl acetic anhydride with cyclopropane ruthenium chloride to obtain Γ-[(5-cyclopropyl) -1,2,4-oxadiazol-3-yl)indolyl] snail [snolo[2,3-f][l,3]benzodioxol-7,3·-峋哚]-2·(1Ή)-one (20%) as colorless solid: mp 136-137 ° C; 1H NMR (300 MHz, CDC13) δ 7.24 (dd, J = 7.7, 7.7 Hz, 1H), 7.17 (d, J = 7.3 Hz, 1H), 7.05 (dd, J = 7.5, 7.5 Hz, 1H), 6.86 (d, J = 7.5 Hz, 1H), 6.48 (s, 1H), 6.30 (s, 1H) , 5.84 (d, J = 3.8 Hz, 2H), 5.00 (ABq, J = 16.4 Hz, 2H), 4.82 (ABq, J = 9.0 Hz, 2H), 2.20-2.09 (m, 1H), 1.21-1.16 ( m, 4H) ; 13C NMR (75 MHz, CDCI3) δ 182.7, 177.3, 165.6, 155.7, 148.9, 142.4, 141.2, 132.3, 128.9, 123.9, 123.8, 119.6, 108.9, 103.5, 101.5, 93.5, 80.2, 58.2, 35.8, 10.50, 10.46, 7.8; MS (ES+) m/z 404.1 (M + 1) 〇 Example 11.25 4'-Gas-anthracene-{[5-(1-mercaptoethyl)_;i,2, 4-oxadiazol-3-yl]methyl} snail [, succinyl[2,3-f][l,3] benzodioxolane _7,3'_+来]_2, (1 buckle_ Ketone synthesis

Follow the procedure as described in Example 11.23, and perform irrelevant changes, replace the trimethylacetic anhydride with gasified isobutyl hydrazine, and use 2_(4ι_chloro- 2, oxa snail [bite 南南和[ 2,3-f][l,3]benzodioxanthene _7χ嗓;|·Γ(2Ή)_yl)_N,·substituting 乙'-hydroxy-2- (2,-keto-6H-spiro[benzofuro[6'5-d][l,3]dioxostenylene_7,3,_dihydroindolyl, yl)imine Indoleamine, 4·-yl-1'-丨[5_(1_mercaptoethyl)_12,4oxadiazol-3-yl]indenyl}spiro[吱,[2,3-f][ l,3] stupid and dioxynene _7,3,_,哚]_2, (1Ή) ketone (26%), colorless solid. Refining point 165-167 ° C; iHNMRGOOMHz 'CDCiy 5 7.19 (dd , J = 8.0, 143924-sp-20091127-4 -706- 201020257 8.0 Hz, 1H), 7.00 (dd, J = 8.2, 0.8 Hz, 1H), 6.77 (dd, J = 7.8, 0.7 Hz, 1H), 6.46 (s, 1H), 6.32 (s, 1H), 5.85 (ABq, 2H), 5.04 (ABq, 2H), 4.95 (ABq, 2H), 3.17 (seven peaks, J = 7.0 Hz, 1H), 1.36 ( d, J = 7.0 Hz, 6H) ; 13C NMR (75 MHz, CDC13) δ 185.2, 177.1, 165.3, 156.7, 149.2, 143.0, 142.1, 131.6, 130.1, 128.4, 124.6, 1 16.5, 107.3, 103.1, 101.5, 93.2, 77.1, 58.8, 36.2, 27.5, 20.1, 20.0; MS (ES+) m/z 440.1 (M + 1). Example 11.26 methylethyl)-l,2,4-oxadiazol-3-yl]methyl}spiro[吱,[2,3-f][l,3] ¥ benzodioxolan Synthesis of -7,3·- 哚 哚]-2\1Ή)-ketone

Ν'-Hydroxy-2-(2·-oxaspiro[唉,[2,3-f][l,3]benzodioxene-7,3,-Θ丨哚]-1' (2Ή)-yl) acetamimidamide (0.35 g, 1.0 mmol) and isobutyric anhydride (250 mL, 1,5 mmol) in pyridine (3 mL), stirred solution Heat at 17 〇C in a microwave reactor for 30 minutes. The solution was concentrated to dryness in vacuo to purified by flash chromatography eluting with ethyl acetate (15% to 50% gradients) , oxadiazole _3_yl) fluorenyl] snail [吱 并[2,3-f][l,3] benzodiox oxalate -7,3,-θ budo]-2' ( 1Ή)-- (0.26 g '64%), as a colorless solid: m.p., i96-199 ° C; 1H NMR (300 ΜΗζ, CDC13) δ 7.28-7.15 (m, 2 Η), 7.05 (dd, J = 7.5 Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.34 (s, 1H), 6.86-6.82 (m, 2H), 5.06 (ABq, 2H), 4.83 (ABq, 2H ), 3.18 (seven peaks, J = 7.0 Hz, 1H), 1.36 (d, J = 7.0 Hz, 6H); 13 C NMR (75 MHz, CDC13) 5 185.0, 177.4, 165.6, 155.7, 148.9, 142.4, 141.2 , 143924-sp-20091127-4 -707- 201020257 132.3, 128.9, 123.9, 123.8, 119.7, 108.9, 103.5, 101.5, 93.5, 80.1, 58.2, 36.0, 27.5, 20.1, 20.0 ; MS (ES+) m/z 406.2 (Μ + 1). Example 11.27 143-(5-Methyl-1,2,4-oxadiazol-3-yl)hanyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b Synthesis of difuran-3,3'4丨哚]-2·(1Ή)-one

Ν·-Hydroxy-3-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b1]difuran-3,3'-啕哚] - Γ (2Ή)-yl) fluorenyl benzoate amide (0.36 g, 0.84 mmol) in pyridine (3 ml), added with vaporized acetonitrile (〇·ΐ 2 ml, 1.68 Millions of ears). The reactants were in a microwave reactor (n〇°C, 200 watts, 200

Stir for 30 minutes in psi). The mixture was concentrated in vacuo. The residue was purified by column chromatography using ethyl acetate ethyl acetate (25% to 40% gradient) eluted from ethyl acetate and diethyl ether to give s-[3-(5-fluorenyl). -1,2,4-oxadiazol-3-yl)benzyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3, - 吲哚]-© 2'(1Ή)-one (0.27 g, 71%) as colorless solid: m.p. </RTI> </RTI> </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; -7.96 (m, 1H), 7.48-7.44 (m, 2H), 7.19-7.12 (m, 2H), 7.03-6.98 (m, 1H), 6.77-6.74 (m, 1H), 6.58 (s, 1H) , 6.42 (s, 1H), 5.18 (d, J = 15.8 Hz, 1H), 5.00 (d, J = 9.0 Hz, 1H), 4.85 (d, J = 15.8 Hz, 1H), 4.72 (d, J = 9.0 Hz, 1H), 4.56-4.50 (m, 2H), 3.07-2.95 (m, 2H), 2.63 (s, 3H); 13C NMR (75 MHz, CDC13) &lt;5 178.0, 176.7, 168.1, 161.9, 161.3, 141.9, 136.6, 132.8, 129.9, 129.6, 128.8, 127.5, 126.9, 126.0, 124.0, 143924-sp-20091127-4 -708- _ (S: 201020257 123.6, 120.2, 120.1, 119.1, 109.2, 93.2, 80.6 , 72.4, 57.8, 43.8, 29.1, 12.4; MS (ES+) m/z 451.8 (Μ + 1). Example 11.28 1'-{3-[5-(Trifluoromethyl)-1,2,4-吟Diazole -3-yl]yote}-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3J-吲哚]-2'(1Ή)-ketone synthesis

The gasification of acetamidine was carried out using trifluoroacetic anhydride according to the procedure as described in Example 11.27, and the change was carried out to obtain trifluoromethyl oxadiazol-3-yl]pinyl}-5,6-di. Hydrogen snail [benzo[i,2-b:5,4-b,]difuran-3,3,-吲哚]-2'(1Ή)- Ming (71%), as colorless solid: mp 182- 188°C ; iHNMRGOO MHz, CDC13) δ 8.12-7.97 (m, 2Η), 7.60-7.51 (m, 2H), 7.25-7.17 (m, 2H), 7.06-7.00 (m, 1H), 6.76-6.72 ( m, 1H), 6.57 (s, 1H), 6.42 (s, 1H), 5.22 (d, J = 15.9 Hz, 1H), 5.00 (d, J = 9.0 Hz, 1H), 4.86 (d, J = 15.9 Hz, 1H), 4.72 (d, J = 9.0 9.0 Hz, 1H), 4.57-4.51 (m, 2H), 3.07-2.92 (m, 2H) ; 13C NMR (75 MHz, CDCI3) δ 178.1, 168.8, 161.9 , 161.4, 141.7, 137.1, 132.8, 131.1, 129.9, 128.8, 127.3, 126.1, 125.6, 124.1, 123.7, 120.2, 120.1, 119.0, 109.1, 93.3, 80.6, 72.5, 65.9, 57.8, 43.7, 29.0, 15.3; MS (ES+) m/z 505.8 (M + 1). Example 11.29 144-(5-Mercapto-4H-1,2,4-triazol-3-yl)benzyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4- b] Synthesis of difuran-3,3'-indole]-2'(1Ή)-one 143924-SP-20091127-4 •709- 201020257

&gt;-CH3 at 4-[(2'-_ base_5,6_:aziro[benzo[U b : 5,4 b,]mn 哚]-r(2'H)-yl)methyl] Benzene f-amine (gram, 〇% millimolar) in a solution of dioxane (15 ml), N,N-dimethylethylamine dimethyl condensate (1.42 ml '9·71 mil) Moore). The reaction was heated to reflux and concentrated in vacuo over EtOAc. To the above residue, acetic acid (15 ml) was added to the mixture of hydrazine monohydrate (0.15 ml, 3.17 mmol). The reaction was quenched with EtOAc (EtOAc (EtOAc m.). Drying with anhydrous sodium sulfate, and filtering. The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with EtOAc from ethyl acetate. ,_[4_(5_曱基-4H-1,2,4-triazol-3-yl)-yl]-5,6-dihydrospiro[benzo[i,2-b: 5,4- b,]difuran-3,3'-吲哚]-▲ 2·(1Ή)-one (0.07 g '16%) as colorless solid: mp 169-180. (: (hexane); 1H NMR ( 300 MHz, CDC13) δ 10.72 (s, 1Η), 8.01 (d, J = 8.1 Hz, 2H), 7.41 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 7.5 Hz, 2H), 7.01 (t, J = 7.5 Hz, 1H), 6.79 (d, J = 7.7 Hz, 1H), 6.45 (s, 1H), 6.40 (s, 1H), 5.19-4.09 (m, 4H), 4.53-4.47 ( m, 2H), 2.95-2.90 (m, 2H), 2.50 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 178.3, 161.9, 161.4, 141.9, 136.9, 132.7, 128.8, 127.8, 126.9, 123.9 , 123.6, 120.0, 119.9, 118.8, 109.4, 93.2, 80.6, 72.4, 57.8, 44.0, 28.9, 11.7; MS (ES+) m/z 450.8 (M + 1). 143924-sp-20091127-4 -710· 201020257 Example 11.30-like-keto-^-dihydrospiro ^Benzene^7: Synthesis of unsatisfactory difuran ^ 哚 哚 ^ ^ beer - based) methyl] benzoic acid

Add lithium hydroxide monohydrate (1.48 g, 35.2 mmol) to 2-[(2'-ketodecyl_5'6-dihydrospiro[benzo[l,2-b:5,4-) b·]Coughane-3,3,-MBu Zhu]-Γ(2Ή)-yl)methyl]benzoic acid methyl ester (6.00 g, 14.2 mmol) in a mixed solvent (tetrahydrofuran / water = 2 / In a solution of 1 ν/ν, 180 ml), stir at ambient temperature for 16 hours. Most of the tetrahydrofuran was removed under vacuum and 15 mL of water was added. The solution was extracted with 50 ml of a mixed solvent (ethyl acetate / hexane: 1/3 ν / ν). The aqueous layer was acidified with IN HCl solution until pH 2. After filtration and air drying, 2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲) was obtained.哚]-Γ(2Ή)-yl)methyl]benzoic acid (5.60 g, 96%) as colorless solid: WNMR (300 MHz, DMSO-d6) δ 13.2 (br s, 1H), 7.95 (dd, J = 7.7, 1.2 Hz, 1H), 7.51 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.37 (dd, J = 7.5, 7.5 Hz, 1H), 7.24-7.14 (m, 2H), 7.12- 6.96 (m, 2H), 6.81 (d, J = 7.7 Hz, 1H), 6.58 (s, 1H), 6.40 (s, 1H), 5.39-5.18 (m, 2H), 4.86 (d, J = 8.9 Hz , 1H), 4.74 (d, J = 8.9 Hz, 1H), 4.47 (t, J = 8.7 Hz, 2H), 3.95 (s, 3H), 2.95 (t, J = 8.7 Hz, 2H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.8, 168.7, 161.6, 161.2, 143.0, 137.6, 133.0, 132.6, 131.5, 129.8, 129.2, 127.7, 126.4, 124.2, 123.6, 120.9, 120.4, 119.7, 109.7, 92.9, 80.5 , 72.6, 57.5, 42.5, 28.8; MS (ES+) m/z 414.0 (M + 1). r 143924-sp-20091127-4 - Knife 1-c: 201020257 Example 11.31 4-[(2'-keto-5,6-dihydrospiro[benzo[12-7:5 4 bi]二味鸣_3 Synthesis of 3, ten flowers]_Γ(2Ή)_yl)methyl]benzoic acid

4-[(2'-keto-5,6-dihydrospiro-I; benzoindole 7:5,4-7,]difuran was used according to the procedure as described in Example 11.30, and the insignificant change was applied. -3,3,-吲»朵]-Γ(2Ή)-yl)mercapto]methyl benzoate substitution 2_[(2,_keto_5,6 dihydrospiro[benzo[l,2- b: 5,4-b']difuran_3,3,-啕哚]-1, (2Ή)-yl)methyl]benzoic acid methyl ester, 4-[(2'-keto-5) ,6-Dihydrospiro[benzo[7:5,4-b']difuran-3,3,-啕嗓Η'(2Ή)-yl)methyl]benzoic acid (95%) as a colorless solid ·· Η Η (3〇〇MHz, CDC13) δ 12.93 (s, 1H), 7.90 (d, J = 8.1 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.22 (dd, J = 7.4 Hz, 1H), 7.16 (d, J = 7.4 Hz, 1H), 7.00 (dd, J = 7.4 Hz, 1H), 6.94 (d, J = 7.4 Hz, 1H), 6.45 (s, 1H), 6.40 (s, 1H), 4.98 (ABq, 2H), 4.77 (ABq, 2H), 4.47 (t, J = 8.9 Hz, 2H), 3.01-2.85 (m, 2H) ; MS (ES+) m/z 414.1 (M+l). Example 11.32 5-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3,_ 哚 哚Synthesis of Η'(2Ή)-yl)methylpyran-2-carboxylic acid

5-[(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene 143924-sp-20091127-4 -712 - 201020257 -8,3'_吲哚H'(2'H)-yl)decyl]furan-2-carboxylic acid oxime ester (1.38 g, 3.17 mmol) and lithium hydroxide (0.76 g, 31.7 m The mixture was stirred at 60 ° C for 2 hours in a mixture of tetrahydrofuran (10 mL) and water (10 mL). The reaction mixture was acidified with hydrochloric acid (5 mL) and extracted with diethylene (3 X 30 mL). The combined organic solution was washed with brine (50 ml), dried over sodium sulfate, and evaporated, and concentrated under reduced pressure to give 5-[(2,-keto-2,3-dihydrospiro[p] Desulphur and [2,3-g][l,4]benzodioxanthene-8,3,-啕哚]-1,(2Ή)-yl)indolyl]pyran-2-carboxylic acid (1.36 g 'quantitative), as colorless solid: mp 2-1951 (diethyl ether); &lt;1H NMR (300 MHz, CDC13) &lt;5 8.40 (br s, 1H), 7.27 (dd, J = 7.8, 7.8 Hz , 1H), 7.25 (d, J = 3.3 Hz, 1H), 7.18 (d, J = 7.5 Hz, 1H), 7.06 (dd, J = 7.5, 7.5 Hz, 1H), 6.94 (d, J = 7.8 Hz , 1H), 6.50 (s, 1H), 6.45 (d, J = 3.3 Hz, 1H), 6.31 (s, 1H), 5.19 (d, J = 16.5 Hz, 1H), 4.92 (d, J = 9.3 Hz , 1H), 4.87 (d, J = 16.5 Hz, 1H), 4.66 (d, J = 9.3 Hz, 1H), 4.21-4.07 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.4, 162.8, 155.2, 154.4, 144.8, 143.7, 141.3, 138.6, 132.3, 129.1, 124.2, 124.0, 121.1, 120.9, 111.8, 110.7, 109.0, 99.5, 80.0, 64,7, 64.0, ® 58.2, 37.5 ; MS (ES+) m /z 419.9 (M + 1) 〇 Example 11.33 N,N-Dimethyl-5-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzene Synthesis of dioxin, terpene-8,3Ί嗓]-1'(2Ή)-yl) fluorenyl] cough _2

5-[(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚Η) '(2Ή)-yl) fluorenyl]pyran-2-carboxylic acid (0.42 g, 1.00 mmol), 143924-sp-20091127-4 -713-201020257 dimethylamine hydrochloride (0.17 g, 2.04 m) Mole), N_(3-dimethylaminopropyl)n, _ethylcarbodiimide hydrochloride (0.26 g, U5 mmol), benzotriazole hydrate (0.21 g, 1.54) A solution of millimolar) and 4-mercaptophyrin (3 ml, 27 mmol) in N,N-dimethylformamide (10 mL) was stirred at ambient temperature for 16 h. The solvent was removed under reduced pressure. EtOAc EtOAc m. The organic phase was further diluted with dichloromethane until all the material was dissolved, then dried over sodium sulfate, and then evaporated and evaporated. Purification by flash column chromatography using dioxindole / decyl alcohol (29:1) to obtain N,N-dimercapto-5-[(2,-keto-2,3-dihydrospiro) [吱吱和[2,3-g][l,4]本一氧氧囷囷-8,3,-4丨p朵]-Γ(2Ή)-yl)methyl]biting_2_ Resveramine (0.34 g, 77%) as colorless solid: mp 224-226. (: (ether/hexane); 1H NMR (300 MHz, DMSO-d6) δ 7.32 (dd, J = 7.5, 7.5 Hz, 1H), 7.22-7.14 (m, 2H), 7.05 (dd, J = 7.8 , 7.5 Hz, 1H), 6.96 (m, 1H), 6.62 (m, 1H), 6.51 (s, 1H), 6.06 (s, 1H), 5.06 (d, J = 16.4 Hz, 1H), 4.97 (d , J = 16.4 Hz, 1H), 4.76 (d, J = 9.3 Hz, 1H), 4.66 (d, J = 9.3 Hz, 1H), 4.22-4.14 (m, 2H), 4.14-4.06 (m, Lu 2H ), 3.05 (br s, 3H), 2.94 (br s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 176.4, 158.9, 154.6, 150.8, 147.2, 144.2, 141.8, 137.8, 131.6, 128.8, 123.6 , 123.3, 121.2, 116.5, 111.0, 109.9, 109.4, 98.8, 79.3, 64.2, 63.6, 57.2, 37.7, 36.7, 35.8 ; MS (ES+) m/z 446.9 (M + 1) o Example 11.34 Γ-(3- Synthesis of propyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-&lt; 哚]-2Χ1Ή)-one Sp-20091127-4 -714- 201020257

Γ-[3-(Benzyloxy)propyl]_5,6-dihydrospiro[benzo-like seven:5,4_bl]difuran-3,3'-pyro]-2·(1Ή)-one (2.70 g, 6.31 mmol) and ι〇% / carbon q gram, 0.94 mmol) in methanol (5 mL) was hydrogenated for 2 hr. The reaction mixture was filtered through a pad of celite. The filtrate was concentrated in vacuo, and the residue was subjected to column chromatography using ethyl acetate (20% to 50% gradient) in hexanes to afford s-(3-hydroxypropyl)-5. 6-Dihydrospiro[benzo[i,2-b: 5,4-b,]difuran-3,3'-indole]-2'(1Ή)-one (2.07 g '97%): Point 54-56 ° C (ethyl acetate / hexane); lH NMR (300 MHz, CDC13) 5 7.33-7.28 (m, 1H), 7.19-7.17 (m, 1H), 7.09-7.04 (m, 1H) , 6.94 (d, J = 9.0 Hz, 1H), 6.45 (s, 1H), 6.41 (s, 1H), 4.77 (ABq, 2H), 4.53 (t, J = 6.0 Hz, 2H), 4.02-3.84 ( m, 2H), 3.63-3.54 (m, 2H), 3.07-2.90 (m, 3H), 1.94-1.83 (m, 2H); MS (ES+) m/z 338.1 (M + 1). Example 11.35 ® 2'--yl-l'-[(2R)-rahydrofuran-2-ylmethyl]-1\2',5,6-tetrahydrospiro[benzo[l,2-b: Synthesis of 5,4-b']difuran-3,3.-吲哚]-4,-carbonitrile

α in 4'-bromo-r-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[{,2-b:5,4-b,]difuran -3,3,-啕哚]-2,(1Ή)-ketone (0.20 g, 0.45 mmol), hexacyanoferrate (II) potassium trihydrate (〇·〇4 g, 〇·1 毫In the turmeric, Ν-二曱基143924-sp-20091127-4 -715· 201020257 in the acetaminophen (5 ml) in the scrambled solution, add acetic acid (π) (〇〇1 g, 0.04耄 Mo ear), then add sodium carbonate (〇克, 〇 9 mmol). The mixture was mixed at 130 C for 18 hours. The mixture was filtered through celite, and the filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate / hexanes '1/2) to give 2'-keto-1'-[(2R)-e9hydrofuran-2-ylmethyl]-i ,, 2',5,6-tetrahydrospiro [stupid [l,2-b : 5,4-b'] diterpene -3,3^ 嗓]-4,-carbonitrile (〇.〇 3 g '16%): NMR (300 MHz, CDC13) 5 7.41-7.25 (m, 3H), 6.46-6.38 (m, 2H), 4.98-4.88 (m, 2H), 4.53 (t, J = 8.7 Hz) , 2H), 4.28-4.15 (m, 1H), 4.03-3.62 (m, 4H), 2.98 (t, J = 8.7 Hz, 2H), 2.14-2.00 (m, 1H), 1.97-1.83 (m, 2H ), 1.74-1.59 ® (m, 1H) ; MS (ES+) m/z 389.0 (M + 1). Example 11.36 2'-keto-r-[(2R)-rahydrofuran-2-ylindenyl]-indole, 2,,5,6-tetrahydrospiro[benzo[l,2-b: 5, Synthesis of 4-b']difuran-3,3,-anthracene-4'-carboxaldehyde

4-Siyl-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Disyl-3,3'-throat]-2'(1Ή)-one (0.80 g, 1'8 mmol) in a stirred solution in anhydrous tetrahydrofuran at -78 ° C, add the first Tri-butyl lithium (2.7 ml, 1.7 M in pentane, 4.5 mmol). The mixture was stirred at -78 C for 45 minutes' followed by the addition of N,N-dimethylformamide (1·4 mL, 18.1 mmol). Make the mixture at _78. (: keep for 30 minutes, then quench the reaction with saturated ammonium hydride solution. Extract with ethyl acetate (3 X 30 ml) 143924-sp-20091127-4 __716

(S 201020257 mixture. The combined organic solution was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate / hexanes 1/2). -yl-l'-[(2R)-tetrazole-2-ylmethyl]-l',2',5,6-tetrahydrospiro[benzo[l,2-b: 5,4_b ,] difuran-3,3,-throindole-4,-carboxycarboxaldehyde (0.19 g, 26%) as colorless solid: iHNMR (300MHz, CDCl3) &lt;5 9.94 (s, 1H), 7.56 (dd , J = 7.8, 1.2 Hz, 1H), 7.45 (dd, J = 7.8, 7.8 Hz, 1H), 7.39-7.33 (m, 1H), 6.42 (s, 1H), 6.41 (s, 1H), 4.98 ( d, J = 9.2 Hz, 1H), 4.86 (d, J = 9.2 Hz, 1H), 4.51 (t, J = 8.7 Hz, 2H), 4.31-4.19 (m, 1H), 4.05-3.66 (m, 4H ), 3.04-2.85 (m, ® 2H), 2.14-2.00 (m, 1H), 1.97-1.83 (m, 2H), 1.77-1.63 (m, 1H); MS (ES+) m/z 392.0 (M + 1) Example 11.37 4'-[(Dimethylamino)methyl H4(2R)-izghydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b: Synthesis of 5,4-b']difuran-3,3W丨哚]-2,(1Ή)-one

In 2'-keto-1'-[(21〇-tetrahydrofuran-2-ylindenyl]-1,,2,,5,6-tetrahydrospiro[benzo[l,2-b: 5,4 -b']difuran-3,3,-anthracene-4,-carboxycarboxaldehyde (0.10 g, 0.26 mmol) and dimethylamine (0.19 ml '0.38 mmol) in di-ethane Sodium triethoxysulfonylborohydride (〇1 gram, 046 mmol) was added to the stirred solution at 0 ° C. The mixture was stirred at ambient temperature for 18 hours and quenched with water. The mixture was extracted with ethyl acetate (3 X 20 mL). The combined organic solution was dried over anhydrous sodium sulfate and then concentrated and evaporated in vacuo. 143924-sp-20091127-4 -717- 201020257 Accept column chromatography (methanol / ethyl acetate, 5 / 100) to give 4,-[(diguanyl) fluorenyl H4(2R)-tetrahydrofuran-2-ylindenyl]-5,6-di Hydrogen snail [benzo[1,2:7:5,4h7]difuran-3,3'-indole]-2'(1'11)-one (0.05 g, 46%) as a colorless solid: 1H NMR (300 MHz, CDC13) δ 7.29-7.20 (m, 1H), 7.07 (d, J = 7.9)

Hz, 1H), 6.98 (t, J = 7.0 Hz, 1H), 6.45-6.39 (m, 1H), 6.38 (s, 1H), 5.07 (dd, J = 8.8, 2.1 Hz, 1H), 4.88 (d , J = 8.8 Hz, 1H), 4.52 (t, J = 8.6 Hz, 1H), 4.33-4.21 (m, 1H), 3.98-3.62 (m, 4H), 3.33 (dd, J = 13.2, 3.3 Hz, 1H), 3.03-2.88 (m, 2H), 2.80 (d, J = 13.2 Hz, 1H), 2.09-1.63 (m, 10H); MS (ES+) m/z 421.0 (M + l). Example 11.38 4'-(Tetrahydropyrrole-1-ylindenyl)-l,-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b : Synthesis of 5,4-b']difuran-3,3,-anthracene-2,(1Ή)-one

Following the procedure as described in Example 11.37, and carrying out irrelevant changes, dimethylamine was replaced with tetrahydropyrrole to obtain 4,-(tetrahydropyrrole-1-ylmethyl)-indole-[(2R)-tetra Hydrogenfuran "South-2-ylindenyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3'-啕哚]-2· (1Ή)-ketone (75%): 4 NMR (300 MHz, CDC13) 6 7.29-7.20 (m, 1H), 7.09 (d, J = 7.9 Hz, 1H), 6.98 (dd, J = 7.0, 7.0 Hz , 1H), 6.45-6.39 (m, 1H), 6.36 (s, 1H), 5.10 (dd, J = 8.8, 2.1 Hz, 1H), 4.87 (d, J = 8.8 Hz, 1H), 4.51 (t, J = 8.6 Hz, 1H), 4.32-4.20 (m, 1H), 3.98-3.62 (m, 4H), 3.58 (dd, J = 13.2, 3.3 Hz, 1H), 3.03-2.89 (m, 3H), 2.40 -1.59 (m, 12H); MS (ES+) m/z 447.1 (M 143924-sp-20091127-4 -718· 201020257 Example 11.39 4'-Amino-14(211)-tetrahydrofuranylmethyl]5 Synthesis of 6_ dihydrospiro[benzo[^7:5'47']difuran-3,3,-啕哚]-2·(1Ή)-_

〇: Reference to anal bromide-r-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro [benzohHb:

5,4 7 ']difuran _3,3'-♦ 朵]_2,(1Ή)__ (〇2〇g, 〇45 mM), benzophenone imine (o.ii ml, 068 mil Mol) and racemic-2,2, bis(diphenylphosphine)-1, hydrazine-hydrazine (〇.1 gram, 〇16 mmol) stirred solution in benzene (5 ml) Inside, ginseng (diphenylmethyleneacetone) dipalladium (9) (〇〇5 g, 〇〇5 mmol) was added, followed by the addition of a third sodium sulphate (〇〇9 g, 〇9 mmol). The mixture was stirred at 90 ° C for 18 hours and filtered through crushed algae. (10) Filtrate in vacuo and the obtained residue was dissolved in THF (15 mL). A solution of hydrazine hydrochloride (2 mL, 2M solution) was added to the mixture. The mixture was stirred at ambient temperature for 3 hours. The mixture was neutralized with sodium bicarbonate solution and extracted with ethyl acetate (3×30 mL). The combined organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (hexane/ethyl acetate, 1/2) to give 4, amine-r-[(2R)-w-hydrofuran-2-ylmethyl]-5,6 dihydrogen Snail [Benzo[12:5,5-7]difuran-3,3'-♦] ketone (7 g, 46%), colorless solid: melting point (10) means °C; 1H NMR (300 MHz, CDC13) 5 7.06 (dd, J = 7.9, 7.9 Hz, 1H), 6.60 (d, J 143924-sp-20091127-4 -719- 201020257 = 10.6 Hz, 1H), 6.48 (dd, J = 7.8, 3.0 Hz, 1H), 6.38 (s, 1H), 6.32 (d, J = 8.2 Hz, 1H), 4.80 (s, 2H), 4.52 (t, J = 8.6 Hz, 2H), 4.33-4.22 ( m, 1H), 3.94-3.62 (m, 4H), 3.59 (s, 2H), 2.99 (t, J = 8.8 Hz, 2H), 2.08-1.80 (m, 3H), 1.78-1.64 (m,1H) ; MS (ES+) m/z 378.8 (M + 1). Example 11.40 and Example 11.41 1·-(moffolin-2-ylindenyl)·5,6-dihydrospiro[benzo[l,2-b:5,4-b,]dioxan-3, 3, _ (five) 哚]-ΑΓΗ)-ketone with l,-[(4-mercapto-morpholine-2-yl)indolyl]-5,6-dihydrospiro[benzo[l,2-b: Synthesis of 5,4-b1]difuran-3,3,-吲哚]-2, (1Ή> ketone

In a steel-shaped container, 1·-[(4-mercapto oxalin-2-yl)methyl]_5,6-dihydrospiro[benzo[l,2-b: 5,4-7, Difuran-3,3,-anthracene-2,(1Ή)-one (0.19 g, 0.41 mmol) was suspended in decyl alcohol (20 mL) and ethyl acetate (2 mL), then added 20% oxidized / carbon (0.03 g, 〇 '〇 4 mmol). The hydrogenation was carried out in a steel bullet-shaped container at 120 psi for 16 hours. The reaction mixture was filtered through a pad of celite, and the filtrate was concentrated to dryness. The residue was purified by column chromatography (ethyl acetate / decyl alcohol / ammonia, WlO.D) to give Γ·[(4 曱 吗 吗 福 啉 么 么 )) methyl]-5,6-dihydro snail [Benzo[1,2-7:5,47']difuran-3,3'-〃5丨哚] ketone (0.015 g, 10%) as a colorless foam, the first soluble fraction: (300 MHz, CDC13) (5 7.34-7.25 (m, 1H), 7.17-6.99 (m, 3H), 6.48 (s, 〇.5H), 6.44 (s, 0.5H), 6.39 (s, 1H), 4.94-4.88 (m, 1H), 4.69-4.63 (m, 1H), 4.52 (t, J = 8.7 Hz, 2H), 4.00-3.55 (m, 5H), 2.97 (t, J = 8.7 Hz, 2H) , 2.76 (d, J = 8.4 Hz 143924-sp-20091127-4 •720- 201020257 1H), 2.60 (d, J = 8.4 Hz, 1H), 2.26 (s, 3H), 2.18-1.88 (m, 2H) 13 C NMR (75 MHz, CDC13) δ 178.1, 178.0, 161.8, 161.7, 161.2, 161.18, 142.7, 142.67, 132.7, 132.6, 128.7, 128.6, 123.7, 123.6, 123.3, 123.2, 120.4, 120.3, 119.8, 119.7 , 118.9, 118.8, 109.6, 109.4, 93.2, 93.16, 80.5, 80.4, 73.7, 73.6, 72.3, 66.8, 66.6, 58.358.0, 57.6, 54.7, 54.6, 46.4, 46.3, 43.2, 43.17, 29.0; MS (ES+ m/z 393.0 (M + 1), with Γ-(morpholine-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2- b: 5,4-b']difuran-3,3'-indole]-2'(1Ή)-one (0.04 g, 26%) as a colorless foam, a second soluble fraction: MS ( ES+) m/z 379.0 (M+l). Example 11.42 Γ-{[4-(1-methylethyl) oxalin-2-yl]methyl}-5,6-dihydrospiro[benzene And [l,2-b : 5,4-b']difuran-3,3·-峋哚]-2'(合成&gt; ketone synthesis

'Addition of 1,-(morpholine·2-ylmethyl)_5,6-dihydrospiro[benzoxene] in a solution of acetone (0.04 ml, 0.53 mmol) in dichloroethane (5 ml) [l,2-b : 5,4-b,] Dipyran-3,3'-吲哚]-2, (1,H&gt;ketone (0.04 g, 0.11 mmol) and triethoxymethoxy Sodium borohydride (0.11 g, 53.53 mmol), then the mixture was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated to dryness and purified and purified Ethyl acetate/methanol/ammonium hydroxide (15/1/〇1), and obtained Γ-{[4-(1-methylethyl)norfosin-2-yl]methyl} 5 6-dihydrogen Snail [benzo[1,2-7:5'47']difuran_3,3W丨哚]-2, (1Ή&gt;-ketone (0.02 g, 54%) as a colorless vesicle; 1 H NMR (3〇〇MHz, CDCl3) 5 7.38_7 25 (m,1Η), 7 18 7 〇4 plus, 143924-sp-20091127-4 •721- 201020257 3H), 6.50 (s, 0.5H), 6.44 (s , 0.5H), 6.41 (s, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.53 (t, J = 8.7 Hz, 2H), 4.00- 3.55 (m, 5H), 2.97 (t, J = 8.7 Hz, 2H), 2.85-2.55 (m, 3H), 2.37-2.03 (m, 2H), 1.0 5-0.98 (m, 6H); MS (ES+) m/z 421.0 (M + 1). Example 11.43 1 -Methyl-5,6-dihydrospiro[benzo[i,2,b:5,4 -b']dipyran-3,3'-ten]-2,(1Ή)- ketone synthesis

On 5,6-dihydrospiro[benzo-like seven:5,4-seven]dioxapyran-3,3·-吲嗓]-2·(1Ή)-one (0.06 g '0.20 mmol) Dissolved in anhydrous ν, Ν-didecyl decylamine (1 〇 ml); added sodium hydride in the solution at ambient temperature (6〇% 'in mineral oil' 0.20 g, 〇.5 〇 莫 )) ^ The mixture was stirred for 15 minutes and added with a portion of hydrazine methane (0.14 g 'ΐ·〇 mmol). The reaction mixture was stirred at ambient temperature for 1 hour then concentrated to dryness. Purification of the residue by flash chromatography using ethyl acetate in hexane (〇% to 30% gradient) to give hydrazinyl-5,6-dihydrospiro[benzo[i,2_b:5 , 4 7 '] dipyran-3,3,-吲嗓]-2,(1Ή)-one (0.06 g '88%): melting point 187-19 (TC; iHNMRGOOMHtCDClJ 5 7.32 (dd, J = 7.4, 7.4 Hz, 1H), 7.17 (d, J = 7.4 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), 6.91 (d, J = 7.4 Hz, 1H), 6.49 (s, 1H), 6.40 (s, 1H), 4.79 (ABq, 2H), 4.52 (t, J = 8.5 Hz, 2H), 3.28 (s, 3H), 2.98 (t, J = 8.5 Hz, 2H) ; 13 C NMR (75 MHz , CDC13) δ 177.7, 161.6, 161.1, 142.9, 132.7, 128.6, 123.6, 123.2, 120.0, 119.7, 118.8, 108.1, 93.0, 80.4, 72.2, 57.6, 28.9, 26.6; MS (ES+) m/z 294.1 143924- Sp-20091127-4 -722- 201020257 (Μ+l). Example 11.44 1,-[4-(1Η-tetrazol-5-yl)benzyl]_5,6-dihydrospiro [stupid and like seven: 5 ,4,7,] Synthesis of difuran-3J-吲哚]-2'(1Ή)-one

In a round bottom flask, packed with 4_[(21-keto-5,6-dihydroindole [benzophenone, 2:7:5,4-7']difuran-3,3'- in toluene (20 ml) θ丨哚]·ι,(2Ή)-yl)methyl]benzine (0.50 g, 1.27 mmol), sodium azide (0.21 g, 3.17 mmol) and triethylamine hydrochloride Salt (0.45 g, 3.17 mmol). The reaction mixture was refluxed under argon for 24 hours. After cooling to ambient temperature, the product was extracted with water. 36% hydrochloric acid was added dropwise to the aqueous layer. The solid was filtered and dried under reduced pressure to give 1'-[4-(1Η-tetrazol-5-yl)-yl]-5,6-dihydrospiro[benzo[l,2-b: 5 ,4-b,]dimethane-3,3W|嗓]-2'(1Ή)-one (0.38 g '58%); 1H NMR (300 MHz, CDC13) 5 φ 8.02 (d, J = 8.0 Hz , 2H), 7.55 (d, J = 8.0 Hz, 2H), 7.22 (t, J = 7.6 Hz, 1H), 7.16 (d, J = 7.6 Hz, 1H), 7.05-6.94 (m, 2H), 6.47 (s, 1H), 6.40 (s, 1H), 5.01 (ABq, 2H), 4.79 (ABq, 2H), 4.53-4.38 (m, 2H), 3.03-2.82 (m, 2H) ; 13C NMR (75 MHz , CD3OD) δ 177.6, 161.6, 161.2, 142.5, 140.1, 132.6, 129.1, 128.6, 127.9, 124.2, 123.6, 120.8, 120.4, 119.4, 109.8, 92.9, 80.3, 72.5, 57.4, 43.3, 28.8; MS (ES+) m/z 437.9 (M + 1). Example 11.45 Γ-(3-Hydroxybenzyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3·-峋哚]-2' Synthesis of (1Ή)-ketone 143924-sp-20091127-4 -723- 201020257

Γ-[3-(Hydroxy)-yl]-5,6-dihydrospiro[benzo[u_b: "seven,]difuran-3,3,-+]-2,_-one ( 1.30 g, 2.7 mmol) and 1% by weight of a mixture of / carbon (25 g) in anhydrous decyl alcohol (14 ml), hydrogenated under a cylinder pressure for 16 hours at ambient temperature. The diatomaceous earth pad is filtered and concentrated to dryness in a vacuum. The residue is subjected to column chromatography (hexane/acetic acid ethyl acetate, from 2:1 to 1:1) to obtain ΐ·-(3-hydroxyl Benzyl)_5,6-dihydrospiro[benzo-like seven:5,4-b,] difuran-3,3·-啕哚]net (0.97 g, 93%), colorless solid: melting point 225 -22TC ; 1H NMR (300 MHz, CDC13) δ 9.48 (s, 1Η), 7.30-7.22 (m, 1H), 7.20-7.11 (m, 2H), 7.06-6.94 (m, 2H), 6.81-6.76 ( m, 1H), 6.72-6.69 (m, 1H), 6.68-6.63 (m, 1H), 6.46 (s, 1H), 6.43 (s, 1H), 4.85 (ABq, 2H), 4.79 (ABq, 2H) , 4.55-4.46 (m, 2H), 3.02-2.92 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 177.0, 161.1, 160.6, 157.6, 142.2, 137.6, 132.0, 129.7, 128.6, 123.6, 123.0 , 120.4, 119.9, 118.9, 117.7, 114.4, 113.6, 109.4, 92.5, 79.8, 72.1, 56.9, 4 2.9, 28.3; MS (ES+) m/z 386.0 (M + 1). Example 11.46 Γ-(4-??p-lin-4-yl-aryl)-5,6-diazaspiro[benzo[l, Synthesis of 2-b: 5,4-b·]di-n--3,3'_吲哚]-2'(1Ή)-ketone 143924-SP-20091127-4 -724- 201020257

Γ-(4-Bromobenzyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b·]difuran_3,3,-吲哚]-2' (1 Ή)-ketone (0.45 g, 1.0 mmol), morphine (0.26 g, 3.0 mmol), dicyclohexyl oxalyl (0.14 g, 0.5 mmol), tetrabutyl a suspension of ammonium sulphate (0.34 g '1 mmol), copper oxide (π) (0.05 g, 0.6 mmol) and carbonic acid planer (0.65 g, 2.0 mmol) in a microwave reactor. Heat at 130 ° C for 1 〇 minutes. The reaction mixture was concentrated under reduced pressure and the residue was subjected to column chromatography using di-hexane-decanol (100: 1-10:1) to give s-(4-fyfolin-4-yl) Indenyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]dipyran-3,3,-θ丨哚]-2·(1Ή)-one, Is a colorless solid: iHNMRpOOMHz 'DCls) δ 7.35-6.74 (m, 8 Η), (0.09 g, 19%), 6.45 (s, 1 Η), 6.41 (s, 1 Η), 4.87 (ABq, 2 Η), 4·81 (ABq, 2H), 4.52 (t, J = 8.7, 8.7 Hz, 2H), 4.01-3.74 (m, 4H), 3.25-3.07 (m, Φ 4H), 3.05-2.90 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 177.8, 161.8, 161.3, 142.1, 132.8, 128.6 (2C), 123.8, 123.3, 120.2, 119.9, 118.9, 116.0, 109.3, 93.2, 80.6, 72.3, 66.6, 57.7, 49.4, 43.6 , 29.0; MS (ES+) m/z 454.87 (M + 1). Example 11.47 Synthesis of 6-Amino-l'-[(2R)-rahydrofuran-2-ylindenyl]spiro[1-benzofuranium]-2'(1Ή)-one 143924-SD-20091127- 4 -725- 201020257

Nh2 at 6-&gt; odoryl-l'-[(2R)'hydrofuran-2-ylindenyl]spiro[丨 并 and furan-3 3,-啕ρ木]-2(1 H)-one (1.65克 '4.1 millimoles), benzophenone imine (〇9〇g, 4 92 moles), ginseng (diphenylarbenium acetonide) dipalladium (9) (〇46g, 〇51mmol) , 2'2'-bis(diphenylphosphino-binaphthalene (〇% g, i 6 mmol) in a stirred solution of toluene (5 mL), adding sodium butoxide ( 〇 55 g, 5 8 mmol.) The solution was heated under reflux for 2 h, cooled to EtOAc EtOAc (EtOAc)EtOAc. The residue was dissolved in tetrahydrofuran (15 mL) and 3M hydrochloric acid (15 mL). The mixture was diluted in ethyl acetate (250 ml) and adjusted to basic with 5M NaOH. Ethyl acetate (2 χ ι〇) </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> Up to 50% gradient ) to give 6-amino-1,-[(2R)-tetrahydrofuran-2-ylindenyl]spiro[1-benzofuran-3,3'-indole]-2'(1Ή)-one ( 0.84 g, 61%), as colorless solid: m.p. 71-74 ° C; 1H NMR (300 MHz, CDC13, mixture of diastereomers) (5 7.29-7.22 (m,1H), 7.14-6.95 ( m, 3H), 6.46 (d, J = 8.1 Hz, 1H), 6.26 (d, J = 2.0 Hz, 1H), 6.10 (dd, J = 8.1, 2.0 Hz, 1H), 4.75 (ABq, 2H), 4.31-4.19 (m, 1H), 3.99-3.61 (m, 6H), 2.08-1.80 (m, 3H), 1.77-1.61 (m, 1H) ; 13 C NMR (75 MHz, CDC13, diastereomer Mixture of substances) 5 178.3 (2), 162.1, 148.4, 142.9 (2), 132.7 (2), 128.6 (2), 123.7, 123.6 (2), 123.2 (2), 118.8 (2), 109.4 (2) , 108.4, 97.2, 80.3 (2), 68.2 (2), 57.6 143924-sp.20091127-4 -726- 201020257 (2), 44.5 (2), 29.1 (2), 25.6 (2); MS (ES+) m/z 337.0 (Μ + 1). Example 11.48 Ν-{2·-_yl-l'-[(2R)_tetrahydrofuran-2-ylmethyl]_Γ, 2,^hydro sulphur benzene benzopyrene-3,3·-吲哚]-6 -Based on the synthesis of methanesulfonamide

• ό 于 6-Amino-(10))-tetrahydrofuran-2-ylmethyl]spiro[1-benzofuran_3,3,^丨嗓]-2'(1Ή)-one (0.20 g' 0.6 Millol), triethylamine (〇.〇9g, 0.9mmol) In the mixed solution of dichloromethane, add gasification 曱 醯 醯 醯 (〇〇7g, 〇, 6m Moore). The solution was stirred at 〇〇c for 4 hours and then concentrated to dryness in vacuo. The residue was purified by flash chromatography using ethyl acetate (50% to 75% gradient) to afford N-{2'-keto-r-[(2R)-tetrahydrofuran. 2-ylmethyl]-1,2-^-a snail [1-benzo-p-propan-3,3'-p?jp]-6-yl}carboxaldehyde-burning amine (0.15 g '61%), *colorless solid: iHNMR (300 MHz, CDCl3) (non-enantiomers) &lt;5 7.75 (d, J = 5.5 Hz, 1H), 7.28 (dd, J = 7.4, 7.4 Hz, 1H), 7.13 -6.97 (m, 3H), 6.75 (dd, J = 8.3, 1.4 Hz, 1H), 6.59-6.42 (m, 2H), 4.93 (d, J = 9.2 Hz, 1H), 4.66 (d, J = 9.2 Hz, 1H), 4.38-4.20 (m, 1H), 3.99-3.64 (m, 4H), 2.92 (s, 3H), 2.16-1.77 (m, 3H), 1.77-1.61 (m, 1H); 13 C NMR (75 MHz, CDC13) (diastereomer) 5 178.2 (2), 161.7 (2), 142.8 (2), 138.9, 131.9 (2), 129.0 (2), 125.0 (2), 124,0 (2) , 123.7 (2), 113.1 (2), 109.8 (2), 102.5 (2), 80.3 (2), 68.2 (2), 57.7 (2), 44.7 (2), 39.2, 25.6 (2); MS (ES+) m/z 415.0 (Μ + 1). Example 11.49 143924-sp-20091127-4 -727· 201020257 Synthesis of 6-hydroxy-indole-(3-mercaptobutyl)spiro[1-benzofuran_3,3W丨哚]ΚΓΗ)-one

6-(Benzyloxy)-1·-(3-methylbutyl)spiro[ι_benzofuran_3,3'-,?丨哚]-oxime)-one (7.80 g, 18.86 mmol) The ear was hydrogenated with a suspension of 1% palladium on carbon (2.00 g, 1.88 mmol) in methanol (150 mL) for 54 hours. The mixture was filtered through a pad of celite. The filtrate was concentrated in vacuo and residue was crystallised from diethyl ether to give 6-hydroxy-indole-(3-mercaptobutyl)spiro[l-benzofuran_3,3i -啕哚]-2,(1Ή)-one (5.20 g, 85%) as colorless solid: m.p.:::::::::::::::::::::::::::::::::::::::::::: , 7.16-7.14 (m, 1H), 7.07-7.02 (m, 1H), 6.92-6.89 (m, 1H), 6.40-6.38 (m, 1H), 6.20-6.12 (m, 2H), 4.77 (AB, 2H), 3.86-3.70 (m, 2H), 1.64-1.59 (m, 3H), 0.99 (d, J = 6.0 Hz, 6H); MS (ES+) m/z 324.3 (M + 1) = Example 11.50 6 -Hydroxy-indole-(3-mercaptobutyl)-5·(trifluoroethyl sulfonyl)spirobenzopyrene _3,3,_(f) 哚]-2'(1Ή)-鲷 synthesis

6-Hydroxy-1H3-methylbutyl) snail U_benzofuran_3,3,吲哚]_2, (1 ketone (1.00 g, 3.10 mmol) in tetrahydro ρ-aramid (30 ml In the mixed solution, add isopropyl magnesium hydride (1·6 ml, 2〇河tetrahydrofuran 143924-SP-20091127-4 -728- 201020257 solution, 3.20 millimolar) at o°c. The mixture was stirred in hydrazine. The mixture was stirred for 1 hour, then trifluoroacetic acid anhydride (0.8 mL, 5.75 mmol) was added. The mixture was stirred at ambient temperature for 52 hours and then quenched with saturated sodium hydrogen carbonate solution and After stirring for 30 minutes, the resulting solution was extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate, and filtered, and the filtrate was concentrated in vacuo. Ethyl acetate in alkane (gradient solution: 10% to 30%) to give 6-hydroxy-indole-(3-methylbutyl)-5-(trifluoroethenyl)spiro[1-benzofuran-3, 3,-啕哚]-2,(1,H)-one (0.12 g, 9%): m.p. 87_88 EtOAc (ethyl acetate / hexane); 4 NMR (300 MHz, CDC13) δ 11.78 (s ,1H), 7.38-7.32 (m, 1H), 7.14-7.03 (m, 3H), 7.07-7.02 (m, 1H), 6.94-6.89 (d, J = 9.0 Hz, 1H), 6.58 (s, 1H), 4.90 (ABq, 2H), 3.95-3.86 (m, 1H ), 3.71-3.62 (m, 1H), 1.66-1.59 (m, 3H), 0.98 (d, J = 6.0 Hz, 6H); MS (ES+) m/z 420.1 (M + 1). Example 11.51 (3R )-3-[(T-keto-indenyl-{[5-(tri-indolyl)furan-2-yl]indolyl}-r,2,-dihydrospiro[1-benzopyran-3 Synthesis of 3'-吲嗓]-6-yl)amino]tetrahydropyrrole_ι_carboxylic acid tert-butyl ester

Cf3

6-Bromo-indenyl-{[5-(trifluoromethyl)furan-2-yl]indolyl}spiro[1-benzofuran-3,3,-indole]-2'(1Ή) -ketone (0.80 g, 1.73 mmol), (R)-l-Boc-3-aminotetrafluoropyrrole (0.48 g, 2.59 mmol) and (2-biphenyl)di-third-butyl Base phosphine (0.08 143924-sp-20091127-4 • 729- 201020257 g '0.28 mmol) in a toluene solution in toluene (15 ml), adding acetic acid (II) (0.09 g '0.14 mmol) )' Then add the third sodium butoxide (0.42 g '4.3 mmol). The mixture was stirred at EtOAc (18 mL). EtOAc (EtOAc) (3R)-3-[(2,-keto-indole-{[5-(trifluoromethyl)pyran-2-yl]indolyl}-indole, 2'-dihydrospiro[1-benzene And 吱3,3,-峋嗓]-6-yl)amino]tetrahydropyrrole-1-carboxylic acid tert-butyl ester (0.47 g, 48%): 1H NMR (300 MHz, CDC13) δ 7.32-7.24 (m, 1H), 7.17 (d, J = 7.4 Hz, 1H), 7.05 (dd, J = 7.4 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.76-6.69 (m , 1H), 6.45 (d, J = 8.2 Hz, 1H), 6.36 (d, J = 3.2 Hz, 1H), 6.19 (d, J = 2.0 Hz, 1H), 6.02 (dd, J = 8.2, 2.0 Hz , 1H), 5.05 (d, J = 16.2 Hz, 1H), 4.95-4.81 (m, 2H), 4.65 (d, J = 9.0 Hz, 1H), 4.00-3.90 (m, 1H), 3.88-3.76 ( m, 1H), 3.73-3.57 (m, 1H), 3.52-3.34 (m, 2H), 3.30-3.11 (m, 1H), 2.23-2.06 (m, 1H), 1.96-1.77 (m, 1H), 1.45 (s, 9H); MS (ES+) m/z 570.2 (M + 1). Example 11.52 6-[(3R)-tetrahydropyrrol-3-ylamino H,-{[5-(trifluoromethyl) (also: sulphur), snail, snail, snail, snail, snail, snail, snail, snail Synthesis

(3R)-3-[(2,-keto-1,-{[5-(trifluoromethyl)pyran-2-yl]methyl}'Γ 2ι_dihydrospiro[1-benzo吱--3,3'-M丨嗓]-6-yl)amino]tetrahydrou-bi-l-hypo-acid third-butyl ester (0.22 g, 0.47 mmol) in methanol (1 mL) In the medium-mixed solution, 4 M vaporized nitrogen (2 ml, 8.0 mmol) in oxanthone was added. Mix 143924-sp-20091127-4 -730- 201020257 and stir at ambient temperature for 16 hours. The solvent and excess hydrogenation are removed under vacuum. The residue was treated with methanol and diethyl ether to afford a solid. After filtration, 6-[(3R)-tetrahydropyrrol-3-ylamino]-indole-{[5-(trifluoromethyl)furan-2-yl]indolyl}spiro[1-benzofuran- 3,3'-啕哚]々'(ΓΗ)-ketone (0.12 g, 47%) as colorless solid: m.p.: s.ss.ssssssssssssssssssssssssssssssssssssssss 7.9 Hz, 1H), 7.26-7.13 (m, 3H), 7.05-6.99 (m, 1H), 6.68 (d, J = 3.2 Hz, 1H), 6.58-6.47 (m, 2H), 6.34 (d, J = 8.2 Hz, 1H), 5.24 (d, J = 16.7 Hz, 1H), 5.05 (d, J = 16.7 Hz, 1H), 4.94 (d, J = 9.1 Hz, 1H), 4.78 (d, J = 9.1 Hz, 1H), ® 4.31-4.24 (m, 1H), 3.67-3.42 (m, 4H), 2.53-2.35 (m, 1H), 2.27-2.11 (m, 1H) ; 13 C NMR (75 MHz, CD3 OD) δ 178.1,162.3 (m), 152.8,141.5,132.2, 128.7, 123.7, 123.6, 123.4, 120.8, 117.3, 112.8 (m), 109.5, 109.1, 79.8, 57.7, 54.2 (m), 49.4, 44.3, 36.3, 29.5; MS (ES+) m/z 470.2 (M + 1). Example 11.53 6-Hydroxy-l'-[(2R)-rahydrofuran-2-ylmethyl]spiro[1-benzofuran- Synthesis of 3,3,-吲哚]-2'(1Ή)-ketone

In r-[(2R)-E3hydrofuran-2-ylmethyl]_6_{[((1-methylethyl)decyl]oxy}spiro[1-benzofuran_3,3,-吲哚]-2'(1Ή)-one (1.69 g, 3.43 mmol) in a solution of anhydrous tetrahydrofuran (15 ml), under nitrogen, a solution of tetrabutylammonium fluoride (1 Μ in tetrahydrofuran, 1 ml, 1 mmol, and the mixture was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated and the residue was crystallised eluted eluted eluted eluted eluted eluted eluted Dehydration drying, filtration, and concentration of β The residue was purified by column chromatography using 40% ethyl acetate in hexane to give 6-hydroxy-r-[(2R)-tetrahydrofuran-2-ylmethyl] Spiro [μbenzofuran_3,3,-吲哚]-2'(1Ή)-one (1.00 g '86%) as colorless solid: m.p. 72-74 ° C; 1H NMR (300 MHz, CDC13) δ 7.29 (ddd, J = 7.5, 7.5, 1.2 Hz, 1H), 7.18-7.01 (m, 3H), 6.80-6.67 (broad, 1H), 6.44 (d, J = 8.4 Hz, 1H), 6.24 (d , J = 2.1 Hz, 1H), 6.17-6.09 (m, 1H), 4.96-4.90 (m, 1H), 4.69-4.63 (m, 1H), 4.36-4.24 (m, 1H), 4.00-3.71 (m , 4H), 2.12-1.61 (m, 4H); MS (ES+) m/z 338.1 (M + 1) 〇 Example 11.54 6-(1-Methylethoxy)-r-[(2R)-E9 Hydrogen Synthesis of furan-2-ylmethyl]spiro[i_benzofuran-3,3·-啕哚]ΚΓΗ)-嗣

Adding bisphosphonium dicarboxylate (under TC and nitrogen) in a stirred solution of diphosphine (0.23 g, 0.89 mmol) in anhydrous tetrahydrofuran (2 mL) 0.14 ml '〇, 89 mmol), isopropanol (〇 23 ml, 2 97 mmol) and 6-hydroxy-l'-[(2R)-tetrahydrofuran-2-ylmethyl] snail fl_ stupid And furan_3 3,(9) 哚]-2'(1Ή)-one (0.20 g, 0.59 mmol). The reaction mixture was stirred at ambient temperature for 16 h then quenched with ammonium chloride solution. The solvent was removed, and the residue was dissolved in ethyl acetate (1 ml), washed with water, brine, dried over sodium sulfate, and filtered, and the filtrate was concentrated to dryness. Purification by chromatography, using 25% ethyl acetate in hexanes to give 6-(1-methylethoxytetrahydrofuran-2-ylmethyl) spiro to benzene 143924-SP-20091127-4-732-201020257 Furan-3,3W丨哚]-2'(1Ή)-one (0.19 g, 85%) as a colorless liquid; 1H NMR (300 MHz, CDC13) δ 7.33-7.25 (m, 1 Η), 7.16-6.99 ( m, 3H), 6.58 (d, J = 8.4 Hz, 1H), 6.50 (d, J = 1.8 H z, 1H), 6.33 (dd, J = 8.4, 2.1 Hz, 1H), 4.93 (d, J = 9.0 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.53-4.43 (m, 1H) ), 4.33-4.23 (m, 1H), 4.00-3.66 (m, 4H), 2.10-1.66 (m, 4H), 1.31 (d, J = 6.0 Hz, 6H) ; MS (ES+) m/z 380.0 ( M + 1), 402.0 (M + 23). Example 11.55 (3S)-3-({2·-keto-l'-[(2R)-rahydrofuran-2-ylmethyl]-1', Synthesis of 2'-dihydrospiro[1-benzoxanium-3,3'-吲哚]-6-yl}oxy)tetrahydropyridin-1-carboxylic acid tert-butyl ester

According to the procedure as described in Example 11.54, and irrelevant changes were made, (3) was replaced with (R&gt; 3-hydroxytetrahydropyrrole-1-carboxylic acid tert-butyl ester to obtain (3S)-3-( {2L keto-l'-[(2R)-whydrofuran-2-ylindenyl]-indole, 2'-dihydrospiro[1-benzofuran-3,3'-吲哚]-6- Tertiary oxy) tetrahydropyrrole-1-carboxylic acid tert-butyl ester (75%), colorless solid: 111]^«1(300]^, €〇&lt;:13) (5 7.33-7.26 (111,111), 7.17-7.00 (m, 3H), 6.64-6.57 (m, 1H), 6.50-6.45 (m, 1H), 6.35-6.28 (m, 1H), 4.94 (d, J = 9.0 Hz , 1H), 4.85-4.78 (m, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.33-4.22 (m, 1H), 4.00-3.40 (m, 8H), 2.22-1.65 (m, 6H ), 1.47 (s, 9H); MS (ES+) m/z 529.1 (M + 23). Example 11.56 6-[(3S)-tetrahydropyrrol-3-yloxy]-1'-[(2R) -iz9hydrofuran-2-ylmethyl]spiro[1-benzofuran-3,3'-吲哚]-2' (1Ή&gt; ketone hydrochloride synthesis 143924-sp-20091127-4 •733· 201020257

HCI is (3S)-3-({2,-_yl-1'-[(HAN)-tetrahydrofuran-2-ylmethyl H,, 2, dihydrospiro & benzofuran-3,3'-呻哚]-6-yl}oxy) tetrahydropyrrolecarboxylic acid tert-butyl ester (0.33 g, 0.65 mmol) in dioxane (5 ml) in a stirred solution, added dioxane 4M hydrogenated hydrogen in sputum (4 ml, 16 mmol). The mixture was stirred at ambient temperature for 3 hours and then anhydrous diethyl ether (m.). A white solid precipitated, which was filtered, washed with diethyl ether and dried to give 6-[(3S&gt;tetrahydropyrrolyloxy)- 14(211)-tetrahydrofuran-2-ylmethyl]spirobenzofuran-3 , 3,-啕哚]-2·(1,Η)-ketohydrochloride (0.24 g, 82%), as colorless solid, melting point 119-121. (: ; iHNMRGOOMHz^DsOD) (5 7.38-7.03 ( m,4H), 6.68-6.59 (m, 2H), 6.48-6.41 (m, 1H), 5.20-5.14 (m, 1H), 4.92-4.85 (m, 1H), 4.73 (d, J = 9.3 Hz, 1H), 4.37-4.24 (m, 1H), 4.00-3.38 (m, 8H), 2.36-1.66 (m, 6H) ; MS (ES+) m/z 407.1 (M + 1) 〇

Example 11.57 (3R)-3-({2'-keto-r-[(2R)-tetrahydrofuran-2-ylmethyl H,,2,^hydrol tl_benzofuran-3,3'-啕Synthesis of 第三]-6-yl}oxy)tetrahydropyrrolecarboxylic acid tri-butyl ester

The (S)-3-hydroxytetrahydropyrrole small carboxylic acid tert-butyl ester was used to replace the isopropanol according to the procedure as described in Example 11.54, and the irrelevant change was carried out to obtain (3R)-3- ({2'-keto-l'-[(2R)-tetrahydrofuran-2-ylmethyl H,,2, dihydrospirophenylene 143924-sp-20091127-4 •734· 201020257 pfu-an-3, 3'-θ丨嗓]-6-yl}oxy)tetrahydropyrrole_methanecarboxylic acid tert-butyl ester (80%), colorless solid: 4 NMR (300 MHz, CDC13) 6 7.34-7.26 ( m,1H), 7.16-7.00 (m, 3H), 6.60 (d, J = 8.1 Hz, 1H), 6.47 (d, J = 2.1 Hz, 1H), 6.32 (d, J = 8.4, 2.1 Hz, 1H ), 4.94 (d, J = 9.0 Hz, 1H), 4.85-4.78 (m, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.33-4.22 (m, 1H), 4.00-3.39 (m, 8H), 2.23-1.65 (m, 6H), 1.47 (s, 9H); MS (ES+) m/z 529.1 (M + 23). Example 11.58

6-[(3R)-ra Hydropyrrole-3-yloxy]-r-[(2R)-rahydrofuran-2-ylmethyl]spiro[l-benzofuran-3,3'-吲哚Synthesis of -2'(1Ή)-ketohydrochloride

Ί^ΙΗ HCI

Using (3R)-3-({2'-keto-r-[(2R)-izg hydrogen hexane-2-ylmethyl] according to the procedure as described in Example 11.56 and performing an insignificant change -ΐ',2'-dihydrospiro[ι_ benzopyrano-3,3'-吲嗓]-6-yl}oxy)tetrahydro ρ ratio slightly _1 times acid third _ (3S)-3-({2'-_yl-l'-[(2R)-E9 hydroquinol-2-ylindenyl]dihydrospiro[i_benzopyran-3,3'-p丨嗓]-6-yl}oxy)tetrahydrop is more specific than _1_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ -1'-[(2 ft)-tetrahydrop-pentan-2-ylindolyl] snail [ι_benzofuran-3,3'-,?丨哚]-2·(1Ή)-one hydrochloride (87%) as colorless solid: m.p. 120-130 °C; 4 NMR (300 MHz, CD3OD) (5 7.38-7.04 (m, 4 Η), 6.68-6.59 (m, 2H), 6.48-6.41 (m, 1H), 5.20-5.14 (m, 1H), 4.92-4.85 (m, 1H) 4.73-4.70 (m, 1H), 4.36-4.24 (m, 1H), 3.99-3.38 (m, 8H), 2.36-1.66 (m, 6H) ; MS (ES+) m/z 407.1 (M + 1) 〇 Example 11.59 143924-sp-20091127-4 -735 - 201020257

3-[(2-_yl-1,2'-dihydrospiro[i_benzoxan]3,3'_4丨嗓]_6-yl)oxy] 3-[(2'-keto) -1'-{[5-(Trifluoromethyl)indolyl]indenyl 4,,2,dihydrospirobenzofuran-3,3'-吲哚]-6-yl) Oxygen Synthesis of tetrahydro, carboxylic acid tert-butyl ester, tetrahydropyrrole-1-carboxylic acid, tert-butyl ester (0 J 9 g, 0.45 mol) in N,N-dimercaptocaramine (10 ml) Sodium hydride (0.02 g '0.54 mmol) was slowly added under stirring in the stirred solution. After 30 minutes, 2-('; odorant thiol)_5_(tri-methyl) p-flavor (0.12 g, 0.54 mmol) was added. The mixture was stirred at ambient temperature for 16 h. then the reaction was quenched with saturated aqueous ammonia (10 mL). The mixture was extracted with ethyl acetate (3 x 20 mL). The combined organic solution was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography (ethyl acetate/hexane, 1/2) to give 3-[(2'-keto-indole-{[5-(trifluoromethyl)pyran-2- Methyl}-indole, 2'-dihydrospiro[1-benzofuran_3,3,_吲哚]-6-yl)oxy]tetrahydropyrrole small carboxylic acid tert-butyl ester (0.14 Gram, 55%), as a colorless solid: 4 NMR (300 MHz, CDC13) (5 7.29 (t, J = 7.7 Hz, 1 Η), о 7.16 (d, J = 7.4 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H), 6.97 (d, J = 7.8 Hz, 1H), 6.76-6.70 (m, 1H), 6.54 (d, J = 8.2 Hz, 1H), 6.47 (s, 1H), 6.40-6.35 (m, 1H), 6.30 (d, J = 8.2 Hz, 1H), 5.06 (d, J = 16.2 Hz, 1H), 4.95 (d, J = 9.0 Hz, 1H), 4.86 (d, J = 16.2 Hz , 1H), 4.80 (br s, 1H), 4.69 (d, J = 9.0 Hz, 1H), 3.64-3.37 (m, 4H), 2.22-1.96 (m, 2H), 1.45 (s, 9H) ; MS (ES+) m/z 593.2 (M + 23). Example 11.60 l'-[(2R)-tetrahydrofuran-2-ylindenyl]spiro[benzo[l,2-b:5,4-b]difuran -3,3'-叼丨143924-sp-20091127-4 -736-

(S 201020257 哚]-2',5(1Ή,6Η)-dione synthesis

({2'-keto-r-[(2R)-iz3hydrofuran-2-ylmethyl]-l,,2,-dihydrospiro-benzofuran-3,3·-吲哚]- 6-yl}oxy)acetic acid (0.42 g, 1.06 mmol) in solution in benzene 'added chlorinated grass mash (0.28 ml, 3.18 mmol) with -drip, Ν_didecyl decylamine Then, the reaction mixture was refluxed for 16 hours. The mixture was evaporated to dryness and dried on a high vacuum pump. The residue was redissolved in anhydrous methane (30 mL), followed by the addition of aluminum trichloride (〇 21 g, 159 mmol). The reaction mixture was stirred at ambient temperature for 16 hours and then refluxed for 2 h. The reaction was quenched by saturated chlorination and then extracted with EtOAc (2 EtOAc). The combined organic phases are dried over sodium sulfate, dried, and purified by flash chromatography eluting with EtOAc EtOAc EtOAc EtOAc Methyl]spiro[benzo[i,2-b:5,4-b,]difuran-3,3, hydrazine]-2',5(1 milk 611)-dione (〇.28克, 69%), as colorless solid: mp 142-144 〇 C; 'H NMR (300 MHz, CDC13) 5 7.36-7.29 (m, 1H), 7.16-7.00 (m, 4H), 6.64-6.60 (m , 1H), 5.08 (d, J = 9.3 Hz, 1H), 4.85-4.80 (m, 1H), 4.61 (s, 2H), 4.31-4.19 (m, 1H), 3.98-3.68 (m, 4H), 2.11-1.84 (m, 3H), 1.76-1.62 (m, 1H); MS (ES+) m/z 377.9 (M + 1), 399.9 (M + 23). Example 11.61 1'-(Tetrahydropyrrol-3-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-oxime哚]-2.(1Ή)-ketone synthesis 143924-sp-20091127-4 •737· 201020257

P According to the procedure described in Example 11.5, and with irrelevant changes, use 3-[(2'-mercapto-5,6-dihydrospiro[benzo[-]],2_b:pfan3 , 3, 奇朵]1 (2 H)-yl)methyl]tetrahydroanthracene]•Several acid, the third butyl group, the replacement of I sing-indolyl-5'6-dihydrospiro[benzo[1, 2 7: 5, 4 7 _] difuran _3, κ 哚 γ (2 ή) _ yl) methyl] /, hydrogen pyridine-1-carboxylic acid second-butyl ester, using tetrahydrofuran to replace di-methane, obtained 1-(tetrahydropyrrol-3-ylmethyl)_5,6-dihydrospiro[benzonb··5,4-7,]furfuran-3,3'-吲哚]-2'(1Ή )-嗣(66%), as a colorless solid: m.p.: 85-95°c (di-carbohydrate) iHNMRGOOMHtCDC^h diastereomers) 7.309 (dd, J = 7.8, 1.2 Hz, 0.5 Hz), 7.305 (dd, J = 7.8, 1.2 Hz, 0.5H), 7.180 (d, J = 7.5 Hz, 0.5H), 7.177 (d, J = 7.5 Hz, 0.5H), 7.063 (dd, J = 7.5, 0.6 Hz , 0.5H), 7.060 (dd, J = 7.5, 0.6 Hz, 0.5H), 6.96 (d, J = 7.8 Hz, 1H), 6.452 (s, 0.5H), 6.450 (s, 0.5H), 6.41 ( s, 1H), 4.92 (d, J = 9.0 Hz, 0.5H), 4.91 (d, J = 9.0 Hz, 0.5H), 4.67 (d, J = 9.0 Hz, 0.5H), 4.66 (d, J = 9.0 Hz, 0.5H), 4.54 (t, J = 8.7 Hz, 2H), 3.85 (dd, J = 14.1, 8.7 Hz, 0.5H), 3.83 (dd, J = 13.8, 7.8 Hz, 0.5H), 3.67 (dd, J = 13.8, 7.5 Hz, 0.5H), 3.65 (dd, J = 13.9, 6.8 Hz, 0.5H), 3.18-2.92 (m, 4H), 2.84-2.65 (m, 2H), 2.55-2.36 (m, 2H), 2.02 -1.89 (m, 1H), 1.67-1.53 (m, 1H); 13C NMR (75 MHz, CDC13) ( diastereomers) 5 178.2, 161.9, 161.4, 142.41, 142.38, 132.9, 128.9, 124.1, 123.5, 120.3, 120.2, 120.1, 120.0, 118.8, 108.7, 93.3, 80.7, 72.48, 72.47, 57.8, 50.4, 46.30, 46.25, 43.41, 43.39, 37.8,29·91,29·86,29.13; MS(ES+) m/z 363.3 (M+l). Example 11.62

143924-sp-20091127-4 -738- (S 201020257 N-(l-decylethyl)-3-[(2·-keto-5,6-dihydrospiro[benzo[Hb:5,4_b] ,] Synthesis of difuran-3,3 - linger]-l'(2'H&gt;yl) fluorenyl] tetrahydropyrrolidine

03⁄4 CH in 1'-(tetrahydropyrrol-3-ylindenyl)-5,6-dioxaspiro[benzo[ubub:5,4-b']difuran-3,3'-1]]- 2'(1Ή)-one (0.24 g '〇·65 mmol) and triethylamine (0.15 mL, 1.1 mmol) in dichloromethane (5 mL) with isocyano-acidic acid Propyl ester (0.10 mL, 1.0 mmol) and the solution was stirred at ambient temperature for 35 min. The reaction was diluted with saturated sodium bicarbonate (4 mL) and EtOAc (EtOAc) The combined organic solution was dried with sodium sulfate, filtered and evaporated. Purification by flash column chromatography using dioxane/diethyl ether (2/1) afforded Ν-(ι·methylethyl) each [(2,-keto- 5,6-dihydrospiro[benzene] And [l,2-b: 5,4-b']dipyran-3,3'-&lt;»5 pulo]-1'(2Ή)-yl)methyl]tetrapyrrole-1-carboxylate Indoleamine (0.24 g, 81%) as a colorless solid: melting point 1 〇 7_115 〇c (hexanes); 1H NMR (300 MHz, CDC13) (diastereomers) 6 7 31 (dd, J = 7.6, 7.6 Hz, 0.5H), 7.30 (dd, J = 7.7, 7.7 Hz, 0.5H), 7.18 (d, J = 6.8 Hz, 1H), 7.07 (dd, J = 7.5, 7.5 Hz, 1H) , 6.90 (d, J = 7.8 Hz, 1H), 6.45 (s, 1H), 6.42 (s, 1H), 4.912 (d, J = 9.0 Hz, 0.5H), 4.906 (d, J =: 8.9 Hz, 0.5H), 4.67 (d, J = 8.9 Hz, 0.5H), 4.66 (d, J = 9.0 Hz, 0.5H), 4.53 (t, J = 8.6 Hz, 2H), 4.03-3.44 (m, 6H) , 3.35-3.17 (m, 2H), 3.00 (t, J = 8.5 Hz, 2H), 2.77 (sevenfold, j = 6.9 Hz, 1H), 2.09-1.98 (m, 1H), 1.87-1.73 (m, 1H), 1.15 (d, J = 5.7 Hz, 3H), 1.14 (d, J = 6.0 Hz, 3H); 13 C NMR (75 MHz, CDC13) (diastereomer) 5 178 33, 178.26, 162.0, 161.4, 156.3, 142.41, 142.36, 132.80, 132.75, 129,0, 124.25, 143924-sp-20091127-4 •739· 201020257 124.23, 123.6, 120.16, 120.10, 120.07, 118.9, 118.8, 108.4, 93.39, 93.36, 80.8, 72.5, 57.8, 49.2, 44.7, 44.6, 42.6, 42.5, 42.43 , 42.40, 37.7, 37.5, 29.35, 29.32, 29.1, 23.7; MS (ES+) m/z 448.2 (Μ+1). Example 11.63 Γ-[(4-mercaptohexahydropyrrol-1-yl)indolyl] snail [吱,[2,3-f][l,3]benzodioxene-7,3 Synthesis of '-吲哚]-2'(1Ή)-ketohydrochloride

Snail [snotic [2,3-f][l,3] benzodioxolanes-7,3'-W哚]-2' (1Ή&gt; class (1.0 g ' 3.6 mmol) , Ν-methylhexahydropyrazine (3.6 g, 36.0 mmol) and formaldehyde (37% by weight solution in water, 2.9 ml, 36.0 mmol) in a stirred solution of methanol for 20 hours. Concentrate to dryness in vacuo, and recrystallize the ether from the hexane to give 1L [(4-methylhexahydropyrylene-1-yl)methyl] sulphide [2, 3-f][l,3]benzodioxanthene-7,3'-吲嗓]-2·(1Ή)-one, a pale orange solid (1.15 g, 81%). Pyridin-1-yl)methyl] snail [bit sulphate [2 jfpj] benzodioxol-7,3'- 吲哚]- oxime)-one (0.50 g, 12.7 mmol) Methanol (10 ml) saturated with hydrochloric acid was added to a solution in methanol (5 ml). The precipitate formed was filtered and dried in vacuo to give Γ[[4-fluorenylhexahydropyridyl)methyl]spiro[吱,[2,3-f][l,3]benzoic Oxytene _7,3,_啕哚]·2, (1ή), hydrochloride (0.65 g 'quantitative), colorless solid: melting point &gt; 175. 〇(decomposition); 1H NMR (300 MHz, DMSO-d6) δ 11.59 (br s, 1H), 9.43 (br s, 1H), 7.41 (d J = 7.9 Hz, 1H), 7.31 (dd, J = 7.6 , 7.6 Hz, 1H), 7.15 (d, J = 6.6 Hz, 1H), 7.〇6 143924-sp-20091127-4 -740- 201020257 (dd, J = 7.4, 7.4 Hz, 1H), 6.66 (s , 1H), 6.47 (s, 1H), 5.89 (s, 2H), 4.86-4.73 (m, 3H), 4.61 (d, J = 9.5 Hz, 1H), 3.54-3.28 (m, 4H), 3.27- 2.94 (m, 4H), 2.71 (s, 3H); MS (ES+) m/z 394.0 (M + 1). For C2 0 H2 3 N3 04 · 2HC1 · 0.5H2 O: C, 55.59; H, 5.51; N, 8.84; found: C, 55.47; H, 5.43; N, 8.78. Example 11.64 (3S)-6-decyloxy-5-methyl-l,-[(4-methylhexahydropyrryl-l-yl)methyl]spiro[i_benzofuran-3J-吲哚]-2\1Ή)-Synthesis of ketone hydrochloride

(3S)-6-decyloxy-5-mercaptospiro[ι_benzocypano- 3,3'_吲嗓]-2'(ΓΗ)-_ (0.50 g '1.8 mmol) , Ν-methylhexahydropyrazine (1,80 g, 17.8 mmol) and mash (37% by weight solution in water, 1.45 ml, 17.8 mmol) refluxed in methanol for 3 hours with stirring solution . The solution was concentrated to dryness in vacuo and dissolved in EtOAc (EtOAc) The solution was again concentrated to dryness in vacuo, dissolved in distilled water (25 mL), and the product was precipitated with 5 NaOH (15 mL). The solid was filtered 'and air dried' to give (3S)-6-methoxy-5-methyl-l,-[(4-mercaptohexahydropyridinyl)methyl]spiro[1-benzofuran. · 3,3,_,嗓]_2,(1Ή)__ (〇65g, 93%). To a stirred solution of the above product (0.20 g) in MeOH (1 mL), EtOAc (EtOAc) , and air-dried, and obtained (3S)_6-methylamino-5-methyl-indole-[(4-methylhexahydropyrazine)methyl]spirobenzofuran 143924-sp-20091127-4 • 741-201020257 4哚]-2'(1Ή)-ketohydrochloride (0.19 g, 71%), as colorless solid: melting point &gt; 2 〇〇 ° C (decomposition); 1H NMR (300 MHz, CDC13) &lt;;5 7.71 (s, 2Η), 7.42 (d, J = 7.9 Hz, 1H), 7.33 (dd, J = 7.5, 7.5 Hz, 1H), 7.17-7.03 (m, 2H), 6.69 (s, 1H) , 6.62 (s, 1H), 4.89-4.70 (m, 2H), 4.65 (d, J = 9.40 Hz, 1H), 3.77 (s, 3H), 3.52-2.91 (m, 5H), 2.72 (s, 3H) , 1.98 (s, 3H); MS (ES+) m/z 394.0 (M + 1); calcd for (: 23 Η 27 Ν 303 · 2.5 Η α · 2.5 Η 20: C, 52.15; H, 6.57; N, 7.93; Found: C, 52.07; H, 6.32; N, 8.50. Example 11.65 (3R)-6-methoxy-5-mercapto-l,-[(4-methylhexahydropyrylene-1-yl) Methyl]spiro[&gt;benzofuran-3,3'-吲哚]-2 (ΓΗ) - Synthesis of ketone hydrochloride

(3R)-6-Methoxy-5-methylspiro[1-benzofuran-3,3,-W哚]-2 was used according to the procedure as described in Example 11.64, and irrelevant changes were applied. , (rH)-keto-substituted (3S)-6-methoxy-5-methylspiro[1-benzofuran-3,3,-indole-2,(indolyl)-one, obtained (3R) -6-methoxy-5-mercapto-indole-[(4-methylhexahydroindol-1-yl)indenyl]spiro[1_benzopyran-3,3Wh]-2' ( 1Ή)-ketohydrochloride (27%) as a colorless solid: melting point &gt; 200 ° C (decomposition); 1H NMR (300 MHz, CDC13) &lt;5 7.57-7.49 (m, 2 Η), 7.39 (d , J = 7.9 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.15-6.99 (m, 2H), 6.65 (s, 1H), 6.59 (s, 1H), 4.87-4.67 (m, 2H), 4.62 (d, J = 9.4 Hz, 1H), 3.73 (s, 3H), 3.51-2.86 (m, 5H), 2.69 (s, 3H), 1.95 (s, 3H) ; MS (ES+) m /z 393.99 (M + 1); calcd for C23H27N303 · 2HC1 · 2H20: C, 54.98; H, 6.62; N, 8.36; Found: C, 54.92; H, 6.33; N, 8.32. 143924-sp-20091127*4 -742- 201020257 Example 11.66 (3S)-1'-[(2R)-e9 Hydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[i,2- b: Synthesis of 5,4-b']difuran-3,3·-吲哚]-2·(1Ή)-one

L'-[(2R)-izg Hydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[i,2-b:5,4-b,]di-f-furan-3, 3'-p?丨哚]-2&quot;(1Ή)-嗣 is analyzed on the palmitic semi-preparative HpLC IA column using 99% tri-butyl decyl ether and 1% acetonitrile. 3S)_r_[(2R)'hydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[1,2-7:5,4-b,]difuran-3,3'-啕哚]-2'(1Ή)-ketone (66%): 4 NMR (300 MHz, CDC13) δ 7.34-6.97 (m, 4 Η), 6.48 (s, 1H), 6.38 (s, 1H), 4.77 (ABq , 2H), 4.50 (t, J = 8.6 Hz, 2H), 4.32-4.21 (m, 1H), 3.92-3.68 (m, 4H), 2.96 (t, J = 8.4 Hz, 2H), 2.10-1.64 ( m, 4H) ; 13C NMR (75 MHz, CDC13) δ 178.2, 161.7, 161.2, 142.8, 132.7, 128.6, 123.6, 123.2, 120.4, 119.8, 118.9, 109.5, 93.1, 80.7, 76.8, 72.3, 68.1, G 57.6 , 44.5, 29.0, 29.0, 25.6, MS (ES+) m/z 363.8 (M + 1). Example 11.67 (3R)-1'-[(2R)-® Hydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran -3J-吲哚]-2'(1Ή)-ketone synthesis

L'-[(2R)-E3 Hydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]di 143924-sp-20091127- 4 -743- 201020257 吱 -3-3,3'-啕哚]-2&quot;(1'11)-ketone is used on the palmitic semi-preparative sub-1^1 column, using a third-butyl methyl ether (99%) was resolved with acetonitrile (1%) to give (3R)_i, _ [(21〇-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[1,2:7: 5,4-1),]difuran-3,3'-mouth bow 1 哚]-2'(1Ή)-ketone (66%) : 4 NMR (300 MHz, CDC13) δ 7.35-6.98 (m, 4H ), 6.47 (s, 1H), 6.38 (s, 1H), 4.78 (ABq, 2H), 4.51 (t, J = 8.6 Hz, 2H), 4.31-4.21 (m, 1H), 3.99-3.63 (m, 4H), 3.03-2.90 (m, 2H), 2.10-1.62 (m, 4H); 13C NMR (75 MHz, CDC13) δ 178.1, 161.7, 161.2, 142.8, 132.6, 128.6, 123.6, 123.2, 120.3, 119.8, 118.8, 109.4, 93.1, 80.6, 76.9, 72.3, 68.2, 57.6.44.6, 29.2, 29.0, 25.5; MS (ES+) m/z 363.8 (Μ + 1). Example 11.68 (3R)-1'-[(2S)-Tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b,]difuran- Synthesis of 3,3'-啕哚]-2'(1Ή)-ketone

L'-[(2S)-Tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-峋哚]-2"(1Ή)-ketone was analyzed on a palmitic semi-preparative HPLC IA column using a third-butyl decyl ether (100%) to give (3R)-r-[(2S) )-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[1,2-7:5,47']difuran-3,3'-吲哚]-2'(1Ή) -ketone (64%): 4 NMR (300 MHz, CDC13) &lt;5 7.32-6.98 (m, 4H), 6.47 (s, 1H), 6.38 (s, 1H), 4.77 (ABq, 2H), 4.51 ( t, J = 8.6 Hz, 2H), 4.31-4.21 (m, 1H), 3.98-3.64 (m, 4H), 3.05-2.88 (m, 2H), 2.09-1.64 (m, 4H); 13C NMR (75 M,,,,,,,,,,,,,,,,,,,,,,,,,,,, 57.6, 44.6, 29.2, 29.0, 25.5; MS (ES+) m/z 363.8 (Μ + 1). Example 11.69 (3S)-14(2S)-tetrahydrofuran-2-ylindenyl]-5,6-dihydro Synthesis of snail [benzo[l,2-b:5,4-b]difuran-3,3'-啕哚]-2&quot;(1)-ketone

T-[(2S)-tetrahydrofuran-2-ylindenyl]-:5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-哚]-2"(1Ή)-嗣 is analyzed on a palmitic semi-preparative HPLC IA column using a third-butyl methyl ether (100%) to give (3S)-1,-[(2S) -tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[{,2-b:5,4-b']difuran-3,3·-&lt;哚]-2Π( 1Ή)-ketone (64%): 1H NMR (300 MHz, CDC13) 3 7.32-6.97 (m, 4Η), 6.48 (s, 1H), 6.38 (s, 1H), 4.77 (ABq, 2H), 4.51 ( t, J = 8.3 Hz, 2H), 4.32-4.21 (m, 1H), 3.91-3.68 (m, 4H), 2.97 (t, J = 8.5 Hz, 2H), 2.10-1.63 (m, 4H) ; 13 C ❹ NMR (75 MHz, CDC13) 5 178.3, 161.7, 161.2, 142.8, 132.7, 128.6, 123.6, 123.2, 120.4, 119.8, 118.9, 109.5, 93.1, 80.6, 76.8, 72.3, 68.1, 57.6, 44.5, 29.0, 25.6 ; MS (ES+) m/z 363.8 (M + 1). Example 11.70 1'-{[(25)-1-Methyl-5-ketotetrahydroindol-2-yl]indenyl}-5 Synthesis of 6-dihydrospiro[benzo[l,2-b:5,4-7|]difuran-3,3·-啕哚]-2'(1Ή)-one 143924-SD-20091127-4 -745 - 201020257

1,1-{[(2S&gt;5-decyltetrahydropyrrole)methyl}·5,6 dihydrospiro[benzo[l,2-b ··5'47']difuran-3 ,3冽哚]-2,(1,Η)-ketone (0.235 g, 〇623 mmol) in a stirred solution in anhydrous Ν'Ν-dimercaptoamine (10 ml) At ambient temperature, sodium hydride (60% in mineral oil, 4 g, 1 4 mmol) was added. The mixture was stirred for 15 minutes and added with iodine (28 g, ❿ 2.0). The reaction mixture was stirred at ambient temperature for 1 hour, and concentrated to dryness. The residue was purified by flash chromatography (hexane / ethyl acetate; gradient: 0% to 30%). ,-{[(2S)-1-methyl-5-ketotetrahydropyrrol-2-yl]methyl}-5,6-dihydrospiro[benzo[l,2-b: 5,4-7 ']二咬喃-3,3,-(9)哚]-2'(1Ή)-one (0.15 g '62%) ' is a colorless solid: melting point 72_76. (: ; hNMRGOOMHz,

CDC13) 5 7.33 (dd, J = 7.5, 7.5 Hz, 1H), 7.20 (d, J = 7.5 Hz, 1H), 7.09 (dd, J

=7.5, 7.5 Hz, 1H), 6.91 (d, J = 7.5 Hz, 1H), 6.46-6.38 (m, 2H), 4.77 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H), 4.03 -3.75 (m, 3H), 3.11-2.83 (m, 5H), 2.61-2.42 (m, 1H), 2.42-2.27 (m, 1H), 2.26-2.07 (m, 1H), 2.03-1.84 (m, 1H); 13 C NMR (75 MHz, CDCI3) δ 178.4, 178.4, 175.1, 175.0, 161.8, 161.3, 161.2, 142.1, 141.9, 132.5, 132.4, 128.9 (2C), 124.3, 124.2, 123.7 (2C), 120.0 , 119.9, 119.7, 119.6, 118.6, 118.5, 108.0, 93.2, 80.5, 72.3, 58.1, 58.0, 57.5 (2C), 43.0, 42.9, 29.3, 29.2, 28.9, 28.7 (2C), 22.6 (2C); MS ( ES+) m/z 391.1 (M + 1). 143924-sp-20091127-4 -746- (8) 201020257 Example 11.71 Γ-[(3-methyl_2-keto-U-tetrahydro-t-sodium _5-yl)methyl] snail [bite mer to [2, 3, benzodioxanthene _7,3'-吲哚]_2, (1, Η) ketone synthesis

1-[(2-keto-1,3-tetrahydrocarbazol-5-yl)indolyl] snail [biting and dioxolan]-7,3·-吲哚]-2, ( 1Ή)-ketone (0.32 g, 0.84 mmol), tetrabutyl bromide (0.05 g, 0.16 mmol), aqueous sodium hydroxide solution (〇(1) g, 2.52 mmol) and dimethyl sulfate ( A mixture of 0.21 g of &lt;RTIgt;&lt;/RTI&gt; The mixture was concentrated to dryness in vacuo. The residue was purified by column chromatography using ethyl acetate (30%) in hexanes to give s-[(3-methyl-2- keto-indole, 3-tetrahydro ρ 嗤-5 -基)曱基] 〇 〇 喃 [2,3-f][l,3] benzodioxolane _7,3,-&gt;»丨❹ 丨❹ beer]-2'(1Ή) -ketone (0.13 g, 40%): m.p. 98-102 ° C; 4 NMR (300 MHz, CDC13) δ 7.39 (dd, J = 7.7, 7.7 Hz, 1H), 7.18 (d, J = 7.4 Hz, 1H ), 7.07 (dd, J = 7.5, 7.5 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.49 (s, 1H), 6.05 (s, 1H), 5.84 (d, J = 6.2 Hz) , 2H), 4.74 (ABq, 2H), 3.93-3.88 (m, 2H), 3.82-3.74 (m, 1H), 2.92 (d, J = 4.0 Hz, 3H), 2.55-2.40 (m, 1H), 2.36-2.26 (m, 1H), 2.20-2.07 (m, 1H), 1.95-1.85 (m, 1H); 13 C NMR (75 MHz, CDC13) δ 178.2, 178.1, 175.2, 175.1, 156.1, 156.0, 149.1 , 142.5, 142.4, 142.2, 142.0, 132.1, 132.0, 129.2, 124.5, 124.4, 123.9, 123.8, 119.0, 118.9, 108.1, 102.8, 102.7, 101.6, 93.8, 93.7, 80.5, 80.4, 58.2, 58.1, 58.0, 57.9 , 43.1, 43.0, 29.3, 29.2, 28.8, 28.7, 22.8, 143924-sp-20091127-5 • 747· 201020257 22.7 ; MS (ES+) m/z 417.3 (M + 1) ° Example 11.7 2

1-{[5-(Di-l-methyl)_1,2,4-oxadiazol-3-yl]methyl} snail|&gt; Fu-Mer [2,3_幻[1,3] 本二Oxygen oxime _7,3'-p?丨嗓]-2'(1Ή)-ketone synthesis in Ν'-hydroxy-2-(2'-oxaspiro[吱,[2,3-f] [l,3] stupid and dioxolene _7,3,_ 啕哚]-Γ(2Ή)-yl) acetammine amide (0.53 g, 1.50 mmol) in dioxane ( In the mixture of 303⁄4 liters, 'in the 〇. Under the lamina, diisopropylethylamine (3 88 g, 3.00 mmol) and trifluoroacetic anhydride (0.41 g, L 95 mmol) were added to afford a clear yellow solution. The reaction solution was stirred for 2 hours. The organic layer was washed with aq. aq. EtOAc (3. The filtrate was concentrated to dryness under reduced pressure. The residue was purified by column chromatography eluting with ethyl acetate (3%) in hexane to afford s-{[5-(trifluoromethyl)-1,2,4-oxadiazole-3 -yl]methyl}spiro[吱,[2,3-f]❹ [1,3]benzodioxol-7,3·-峋哚]-2'(1Ή)-one (0.47克, 73%), as colorless solid: mp 139-140 〇 C; 1H NMR (300MHz, DMSO-d6) δ 7.30 (ddd, J = 7.7, 7.7, 1.2 Hz, 1H), 7.19 (d, J = 7.4 Hz , 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.05 (ddd, J = 7.5, 7.5, 0.8 Hz, 1H), 6.67 (s, 1H), 6.23 (s, 1H), 5.89 (d, J = 3.8 Hz, 2H), 5.28 (ABq, 2H), 4.74 (ABq, 2H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.1, 167.8, 165.5 (d, 2 JCF = 42 Hz), 155.7 , 148.9, 142.2, 141.8, 132.1, 129.3, 124.2, 124.0, 120.2, 116.1 (d, 1JCF= 273 Hz), 109.9, 103.5, 101.9, 143924-sp-20091127-5 -748- 201020257 93.8, 79.9, 57.9, 35.9 ; MS (ES+) m/z 432.2 (Μ + 1). Example 11.73 Ν-Isopropyl-3-[2-(2'-oxaspiro[吱,[2,3-q[l,3]benzodioxyl]_7,3,_吲哚] Synthesis of Γ(2Ή)-yl)ethyl]hexahydropyridine-1-carboxyguanamine

In l'-(2-hexahydropyridin-3-ylethyl)spiro[唉2[3,3-f][l,3]benzodioxol-7,3·-啕哚2·(1Ή)-one (0.82 g, 2.09 mmol) and diisopropylethylamine (1.08 g ' 8.37 mmol) in a mixture of anhydrous dichloromethane (25 mL) Isopropyl isocyanate (0.36 g, 4-18 mmol) was added at 0 °C. The reaction mixture was stirred at ambient temperature for 16 hours. The reaction was quenched by the addition of a saturated aqueous solution of ammonium chloride (100 mL) and was then evaporated. The combined organic solution was washed with brine (8 mL) dried over anhydrous sodium sulfate sulfate, filtered, and evaporated. The residue was purified by column chromatography using methanol (2% to 1% gradient) in di-methane to give N-isopropyl- 3-[2-(2,- oxo[[ And [2,3-f][l,3]benzodioxol-7,3'-W哚]-i'(2'H)-yl)ethyl]hexafluoropyridine-1-carboxylate Indoleamine (0.21 g, 21%) 'is a colorless solid. · m.p. 2 〇 6 〇 〇 8 〇c (ethyl acetate/hexane ihnmr (300 MHz, DMSO-de) δ 7.34 (ddd, J = 7.8, 7.8, 1.0 Hz, 1H), 7.16 (dd, J = 6.4, 6.4 Hz, 2H), 7.05 (dd, J = 7.3, 7.3 Hz, 1H), 6.69 (s, 1H), 6.16 (s, 1H), 5.97 ( d, J = 7.6 Hz, 1H), 5.92 (s, 2H), 4.77 (d, J = 9.3 Hz, 1H), 4.66 (d, J = 9.3 Hz, 1H), 3.84-3.60 (m, 5H), 2.66 (t, J = 10.7 Hz, 1H), 2.55-2.47 (m, 1H), 143924-sp-20091127-5 -749- 201020257 1.85-1.81 (m, 1H), 1.57-1.10 (m, 6H), 1.03 (d, J = 6.6 Hz, 3H), 0.97 (d, J = 6.6 Hz, 3H); 13 C NMR (75 MHz, DMSO-d6) δ 176.6, 156.5, 155.4, 148.2, 142.2, 141.7, 131.9, 128.9, 123.6, 122.9, 119.7, 109.0, 102.8, 101.4, 93.3, 79.8, 57.4, 48.8, 43.9, 41.7, 37.5, 33.0, 30.6, 30.5, 24.4, 22.9, 22.8; MS (ES+) m/z 478.5 (M + 1) tamping 11.74 5-[(2'-Oxospiro[2,3-f][l,3]benzodioxol-7,3'-p5丨哚]_i'(2'h) - base) thiol &gt; synthesis of cephene-3-carbonitrile

Γ-[(4-Mothyl-2-pyrimenyl) fluorenyl] snail [吱,[2,3_叩,3] benzodioxolan-7,3'-峋哚]- 2'(1Ή)-one (0.456 g, 1.0 mmol) and cyanide (0.117 g '1.0 mmol) in a suspension mixture in anhydrous ν, Ν-dimercaptocaramine (5 mL) Add 肆 (triphenylphosphine) to put (〇〇 4 g, 〇〇 3 mmol). The reaction mixture was placed in a microwave reactor set at 1 Torr and placed at 133 ° C for 7 minutes. The solid was filtered and washed with ethyl acetate (4 mL). The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography using ethyl acetate (10% to 30% gradient) of hexanes to give 5 7.2 s ox snails [2,3-f][l , 3] benzodioxanthene _7,3,_吲哚]_Γ(2Ή)_yl) fluorenyl] sulfoxime _3 phthalonitrile (0.25 g, 62%), colorless solid: melting point 2〇 7_2〇9. (: (dioxane / hexane); 1H NMR (300 MHZ, DMSO-d6) 5 8.48 (d, J = 1.3 Ηζ, 1 Η), 7.63 (d,

J = 1.3 Hz, 1H), 7.33 (dd, J = 7.8, 1.1 Hz, 1H), 7.23-7.19 (m, 2H), 7.06 (d, J = 7.4, 0.8 Hz, 1H), 6.71 (s, 1H) ), 6.15 (s, 1H), 5.93 (d, J = 1.5 Hz, 2H), 5.14 (d, J 143924-sp-20091127-5 -750- 201020257 =4.6 Hz, 2H), 4.81 (d, J = 9.4 Hz, 1H), 4.69 (d, J = 9.4 Hz, 1H); 13 C NMR (75 MHz, DMSO-i^) δ 176.5, 155.4, 148.3, 141.7, 141.5, 141.3, 137.8, 131.5, 128.8, 127.9 , 123·7, 123.3, 119.4, 115.1, 109.3, 108.7, 102.8, 101.4, 93.3, 79.7, 57.3, 37.9; MS (ES+) m/z 403.2 (Μ + 1). Example 11.75 2·-keto-anthracene dihydrospiro [bito-and-[2,3-f][l,3]benzodioxanthene-7,3,-吲哚]-7'-carbonitrile Synthesis

7'-Bromo-spiro[吱,[2,3-f][l,3]benzodioxol-7,3,-吲哚]-indole)-one (0.44 g, 1.2 m Mol) and cyanide (0.28 g, 2.4 mmol) in a suspension mixture of anhydrous hydrazine, hydrazine-didecyl decylamine (12 ml), adding hydrazine (diphosphine) (0.14 g, The reaction mixture was refluxed for 3 hours at 0.12 mmol. The solid was filtered and washed with ethyl acetate (40 mL). The filtrate was concentrated to dryness in the vacuum. The residue was purified by column chromatography using ethyl acetate (20% to 30% gradient) in hexane to give 2,- keto-indole, 2,-dihydrospiro[2] , 3-f][l,3]benzodioxanthene-7,3·-,5丨哚]-7,-carbonitrile (0.28 g, 76%), as colorless solid: mp 205-207 °C ; 1H NMR (300 MHz, DMSO-d6) δ 11.55 (s, 1H), 7.62 (dd, J = 8.0 Hz, 1.1 Hz, 1H), 7.41 (d, J = 7.0 Hz, 1H), 7.12- 7.07 (m, 1H), 6.69 (s, 1H), 6.44 (s, 1H), 5.93 (dd, J = 3.4, 0.8 Hz, 2H), 4.78 (d, J = 9.5 Hz, 1H), 4.67 (d , J = 9.5 Hz, 1H) ; 13 C NMR (75 MHz, DMSO-d6) δ 178.4, 155.4, 148.3, 145.2, 141.7, 133.8, 131.6, 128.3, 122.5, 118.9, 115.9, 103.2, 101.3, 93.1, 92.6 , 79.6, 57.5; MS (ES+) m/z 307.3 (M + 143924-sp-20091127-5 -751- 201020257 Example 11.76 (2'-keto-2,3-dihydrospiro[吱β南和[2 ,3-g][l,4]benzoxaoxide round thin _8,3'-p-b j 哚]-Γ(2Ή)-yl)

According to the procedure as described in Example 11.30, and with irrelevant changes, use (π-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzophenan Oxygen-based ortho-salt-8,3·-嘀哚]-Γ(2Ή)-yl)acetate-acetate replacement of 2-[(2,-keto-5,6-dihydrospiro[benzo[1'2- b: 5,4-b']difuran-3,3'-吲哚]-1'(2Ή)-yl)methyl]benzoic acid methyl ester, (21-keto-2,3-dihydrogen) Snail [Miso-[2,3-g][l,4]benzodioxanene_8,3,_ 4 哚]-Γ(2Ή)-yl)acetic acid (83%): melting point 193- 196. . (water); 4 NMR (3〇〇MHz, DMSO-d6) 5 7.26-7.21 (m, 1H), 7.09-7.07 (m, 1H), 6.99-6.91 (m, 2H), 6.45 (s, 1H) , 6.27 (s, 1H), 4.66 (ABq, 2H), 4.29-4.05 (m, 6H); MS (ES+) m/z 353.7 (M + 1). Example 11.77 Γ-Methyl-2'-keto-1',2,2',3-tetrahydrospiro[吱,[2,3-phan [1,4]benzodioxanthene-8 , 3^5丨哚]_4'_carboxylic acid synthesis

Γ-Γ-yl-2'--yl-l',2,2,3-trihydrospiro[吱,[2,3-g][l,4]benzodiazepine-8 , 3'-M丨哚]-4'-acid phenyl ester (2.00 g, 4.65 mmol) in tetrahydrofuran 143924-sp-20091127-5 • 752- 201020257 cum (50 ml) with water (10 ml Lithium hydroxide monohydrate (1.00 g, 23.8 mmol) was added to the solution in the solution at ambient temperature. The reaction mixture was stirred at ambient temperature for 18 h and concentrated in vacuo. The residue was neutralized to pH 4-5 with 10% w/v hydrochloric acid. The formed sediment was filtered and washed with diethyl ether to give 1,-methyl-2,-keto-oxime, 2,2',3-tetrahydrospiro[2,3-g ][l,4]benzodioxanthene-8,3'-β哚]-4'-carboxylic acid (1.40 g, 85%): melting point 297-299 °C; ^ NMR (300 MHz, DMSO -de) 5 7.54-7.43 (m, 3H), 7.32-7.28 (m, 1H), 6.31 (s, 1H), 6.03 (s, 1H), 4.77 (ABq, 2H), 4.12-4.02 (m, 4H ), 3.15 (s, ® 3H) ; MS (ES+) m/z 376.0 (M + 23). Example 11.78 34(3-Bromopyridin-2-yl)indolyl]-2,3-dihydrospiro[1,3-g][l,4]benzodioxanene-8 ,1'-茚]-2·(3Ή)-ketone synthesis

(3-Bromopyridin-2-yl)nonanol (0.100 g, 〇.53 〇 mmol) with sulfinium dichloride (0.070 mL, 0.97 mmol) in dichloromethane (3 mL) The mixture with hydrazine, hydrazine monomethylamine (1 drop) was stirred at ambient temperature for 16 hours. The reaction mixture was concentrated in vacuo and THF (5 mL) &lt;RTIgt;&lt;RTIID=0.0&gt;&gt; 3 phantom [1,4] benzodioxene _8,3,_吲哚]_2, (1 Ή) ketone (〇121 g, 〇41 mmol), carbonic acid planer (0.374 g, 1.15 mmol) Ear) and potassium iodide (〇〇38 g, 〇23 mmol). The mixture was heated for 1 hour at 1 Torr and allowed to cool to ambient temperature 143924-sp-2009 1127-5 - 753 - 201020257 and concentrated in vacuo. The residue was successively triturated with water and decyl alcohol, and further purified by column chromatography, and eluted with ethyl acetate in a 0% to 50% gradient in methane to give 3'-[(3-bromo) Pyridin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,1·-茚]- 2'(3Ή)-_ (0.113 g, 59%) as colorless solid: mp 217-218 ° C; 4 NMR (300 MHz, DMSO-d6) δ 8.41 (d, 1 Η, J = 4.0 Hz), 8.15 (d, J = 8.1 Hz, 1H), 7.24 (m, 1H), 6.50 (s, 1H), 6.43 (s, 1H), 5.13 (ABq, 2H), 4.75 (ABq, 2H), 4.14-4.09 ( m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.3, 155.0, 152.6, 148.3, 144.6, 143.3, 141.3, 138.2, 132.4, 129.1, 125.1, 123.9, 123.3, 122.1, 120.2, 112.3, 109.7, 99.0, 79.7, 64.7, 64.1, 57.7, 44.7; MS (ES+) m/z 464.6 (M + 1), 466.6 (M + 1). Example 11.79 3 -{[3-(曱 酿 )) p is more than -2-yl]methyl}-2,3-dihydrospiro [biting π Nanhe [2,3_g][i,4] benzo Synthesis of Dioxinene-8,Γ-茚]-2'(3Ή)-ketone

3-[(3-Bromo-p-pyridin-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][i,4]benzoxa-oxygen Rare-8, Γ-section]-2'(3Ή)-ketone (0.233 g, 〇.5 〇 millimolar), sodium sulfonate (0.071 g, 0.60 mmol), copper iodide (〇. 〇10g, 〇〇5mmol) and a mixture of L-proline sodium salt (0.014g, 〇.1〇 mmol) in a diterpene stone (1 ml) combined with '95 Heat at ° C for 48 hours and then at ambient temperature for 30 hours. The reaction mixture was diluted with ethyl acetate (5 mL), EtOAc EtOAc EtOAc (EtOAc) The residue was triturated from methanol and further purified by column chromatography and eluted with ethyl acetate in dichloromethane from 5% to 50% to give the methanesulfonyl. }}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,1,_茚]_2,(3Ή)-one (0.103 Gram, 44%), as colorless solid: mp. &lt;250 °C; iHNMRGOOMHz 'DMSO-c^) 6 8.69 (d, J = 4.2 Hz, 1H), 8.35 (dd, J = 8.0, 0.5 Hz, 1H) , 7.64 (dd, J = 7.9, 4.7 Hz, 1H), 7.24 (dd, J =: 7.7, 7.7 Hz, 1H), 7.18 (d, J = 7.3 Hz, 1H), 7.05-6.99 (m, 2H) , 6.50 (s, 1H), 6.39 (s, 1H), 5.50 (ABq, 2H), 4.76 (ABq, 2H), 4.19-4.12 (m, 4H), 3.52 (s, 3H) ; 13C NMR (75 MHz , DMSO-d6) &lt;5 177.6, 155.0, 153.7, 153.6, 144.6, 143.4, 138.4, 138.2, 135.9, 132.4, 129.1, 124.1, 123.9, 123.3, 122.1, 112.2, 109.8, 99.1, 79.6, 64.7, 64.1, 57.7, 44.2, 42.7; MS (ES+) m/z 465.0 (Μ +1). Example 11.80

2-[(2'-keto-2,2',3,3'-tetrahydrospiro[Blowing] Nanhe [2,3-g][l,4]benzodioxanthene-8 Γ-茚]-3·-yl) fluorenyl> Synthesis of pyridine-3-carbonitrile

3·-[(3-Bromopyridin-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,1·-茚]-2'(3Ή)-ketone (0.233 g, 0.500 mmol), vaporized nickel (ruthenium) hexahydrate (0.113 g, 0.500 mmol) and sodium cyanide (0.050) Gram, 1, 〇mole) was combined in 1-mercapto-2-tetrahydrofuranone (1 mL) at 2 Torr. 〇 143924-sp-20091127-5 •755· 201020257 'heated under microwave irradiation for 30 minutes. The reaction mixture was cooled to mp EtOAc (EtOAc)EtOAc. The combined organic layers were washed with brine (3×20 mL) dried over sodium sulfate. The resulting residue is subjected to column chromatography and eluted with a gradient of 50% to 75% of ethyl acetate in hexane to give 2-[(2'-keto-2,2,3, 3: tetrahydrospiro[吱,[2,3-g][l,4] benzodioxan-8, Γ-茚]-3'-yl) fluorenyl]pyridine-3-carbonitrile (0.593 g, 29%), as colorless solid: m.p. 230-233°C; 1HNMR (300 MHz, DMSO-d6) 5 8.71 (dd, J = 4.8, 1.4 Hz, 1H), 8.38 (dd, J = 7.9, 1.5 Hz, 1H), 7.56 (dd, J = 7.8, 4.9 Hz, 1H), 7.27-7.15 (m, 2H), 7.04 (d, J = 7.5 Hz, 1H), 6.98 (d, J = 7.9 Hz, 1H), 6.50 (s, 1H), 6.38 (s, 1H), 5.30 (s, 2H), 4.74 (ABq, 2H), 4.19-4.11 (m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.3, 158.2, 155.0, 153.1, 144.6, 143.1, 142.1, 138.2, 132.4, 129.1, 124.0, 123.4, 121.9, 116.5, 112.2, 109.8, 108.0, 99·1, 79.8, 64·7, 64.1, 57.7, 44.1 MS (ES+) m/z 412.0 (M + l). Example 11.81 (8S)-l'-{[3-efluoroindolyl>pyridin-2-yl]methyl}_2,3_dihydrospiro[吱,[2,3-g][l, 4] Synthesis of benzodioxanthenium _8,3'_qiao丨嗓]_2, (1,H)-ketone

Using (8S)-2,3-dihydrospiro[,,,,,,,,,,,,,,,,, 2,3-dihydrospiro[2,3-f][l,4]benzodioxanthene 143924 -sp-20091127-5 -756- 201020257 ene-7,3'-吲哚]-2'(1Ή)-one, and replaced with 3-(difluoromethyl)pyridin-2-yl]methanol hydrochloride (3-(Trifluoromethyl)pyridin-2-yl)nonanol hydrochloride, (8S)-l'-{[3-(difluoromethyl)pyridin-2-yl]methyl}-2 ,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one (50%) , as a colorless solid: mp 181-182 〇 C; 1H NMR (300 MHz, DMSO-d6) δ 8.56 (d, J = 4.9 Hz, 1H), 8.08 (d, J = 7.7 Hz, 1H), 7.52-7.50 (m, 1H), 7.52-7.42 (m, 1H), 7.25-7.15 (m, 2H), 7.01 (dd, J = 7.5, 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.42 (s, 1H), 5.18 (ABq, 2H), 4.72 (ABq, 2H), 4.19-4.12 (m, 4H) ; 13C NMR (75 ® MHz, DMSO-d6) δ 111 A, 155.0, 152.9 (t, JC.F = 4.3 Hz), 151.4, 144.6, 143.2, 138.2, 135.0 (t, JC.F = 7.0 Hz), 132.5, 129.1, 128.0 (t, JC.F = 22.6 Hz), 123.9, 123.5, 123.3, 122.0, 113.8 (t, Jc-f= 236.6 Hz), 112.3, 109.7, 99.1, 79.7, 64.7 ,64.1,57.8,42.3; MS (ES+) m/z 436.9 (M + 1) 〇 Example 11.82 K hydroxy-34 (2^-keto-2,3-dihydrospiro[唉,[2,3- g][l,4] Synthesis of benzodioxanthene-8,3'-M丨嗓]-1'(2Ή)-yl)methyl]benzene resoleimide

3-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,3'-吲哚] -Γ(2Ή)-yl)methyl]benzonitrile (〇.4〇克, 0.98 mmol) in a solution of dimethyl amide (ίο ml) 'Addition of hydroxylamine (5〇% w in water) /w solution, 0.66 ml, 10.7 mmol. The reaction was stirred at 8 ° C for 3 hours and allowed to cool to ambient temperature. Water is added to cause sediment deposition. By 143924-sp-20091127-5 -757- 201020257, the solid was collected by filtration and washed with water to give Ν'-hydroxy-3-[(2'-keto-2,3-dihydrospiro[furan[ 2,3-g][l,4]benzodioxanthene-8,3·-(9)哚]-Γ(2Ή)-yl)indolyl]benzoateimine amide (〇·4〇)克, 93%) : 1H NMR (300 MHz, CDC13) δ 7.98 (br s, 1H), 7.64 (s, 2H), 7.43-7.38 (m, 4H), 7.15-7.11 (m, 2H), 7.01- 6.96 (m, 1H), 6.79 (s, 1H), 6.67-6.64 (m, 1H), 6.49 (s, 1H), 5.33-5.28 (m, 1H), 4.96-4.58 (m, 3H), 4.19- 4.16 (m, 4H) ; MS (ES+) m/z 444.0 (M + 1). Example 11.83 l'-[3-(5-Mercapto-1,2,4-oxadiazol-3-yl)henyl]-2,3-dihydrospiro[Ethrano[2,3-§] [1,4] Synthesis of benzodioxanthene-8,3'-吲哚]-2'(1 ugly)-ketone

According to the procedure as described in Example 11.27, and with irrelevant changes, use Ν'-carbyl-3-1X21-keto-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene-8,3'-吲哚]-Γ(2Ή)-yl) fluorenyl] benzoquinone imine guanamine replacement Ν'-hydroxy-3-[(2: Keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-...❿ 哚]-1'(2Ή)-yl) fluorenyl Benzene carboxy quinone imine amide, obtaining ι·-[3-(5-fluorenyl-1,2+ oxadiazol-3-yl)-yl]-2,3-dihydrospiro[吱 并[ 2,3-g][l,4]benzodioxanthene-8,3'-indole]-2'(1Ή)-one (65%) as colorless solid: mp 90-95 ° C (ethyl acetate / diethyl ether); 111 ruler (300 ^ 11 ^, 匚〇 (: 13) 5 7.89-7'87 (111, 211), 7.58-7.53 (m, 2H), 7.25-7.15 (m, 2H), 7.03-6.95 (m, 2H), 6.50 (s, 1H), 6.20 (s, 1H), 5.15-4.64 (m, 4H), 4.16-4.07 (m, 4H), 2.62 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 178.1, 177.3, 167.8, 155.2, 144.7, 142.4, 138.4, 137.9, 132.2, 143924-sp-20091127-5 - 758 - (s) 201020257 130.8, 130.2, 129'3 , 127.2, 126.3, 125.5, 124.2, 123.7, 121.5, 111.6, 109.9, 99.3 , 80.0, 64·7, 64.0, 57.8, 43.1, 12.4; MS (ES+) m/z 467.8 (M + l). Example 11.84 Γ-[4-(5-methyl_i, 2, 4) Diazol-3-3-motyl]_2,3_dihydrospiro[吱,[2,31][1,4]benzodioxolene_8,3'-吲哚]-2' ( Synthesis of 1,11)-ketone

4-[(2·-keto-2,3-dihydrospiro[2,3-g][l,4] benzodioxanthene-8,3·-吲哚Η '(2Ή)-yl)methyl]benzonitrile (0.41 g, 1. 〇 mmol) in a solution of diterpenoid (20 ml) with hydroxylamine (5 〇% w/w in water) Solution '2.0 ml '33 mmol). The mixture was heated at 8 (TC for 16 hours, allowed to cool to ambient temperature and diluted with water (5 mL), causing a precipitate to precipitate. The solid was collected by filtration and in a 1 liter microwave reaction vessel with hydrazine Pyridine (2_0 ml) and acetic anhydride (0.2 g, 2, 〇 millimol) were combined. The mixture was heated at 17 ° C for 15 minutes under microwave irradiation, allowed to cool to ambient temperature, and under vacuum Concentration in the residue. Purify the residue by column chromatography and elute with ethyl acetate in 15% to 50% gradient in hexane to give decyl-1,2'4-oxadiazol-3-yl. Yuji]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,3'-θ丨嗓]-2'(1Ή )-ketone (0.52 g, 85%) as colorless solid: m.p. 174 - 175 ° C (ethyl acetate / hexane); iH NMR (300 MHz, DMSO-d6) &lt;5 8.06-8.00 (m, 2H ), 7.42 (d, J = 8.3 Hz, 2H), 7.22-7.13 (m, 2H), 7.04-6.97 (m, 1H), 6.75 (d, J = 7.7 Hz, 1H), 6.50 (s, 1H) , 6.23 (s, 1H), 5.12 (d, J = 15.8 Hz, 143924-sp-20091127-5 -759· 201020257 1H), 4.94 (d, J = 8.9 Hz, 1H), 4.85 (d, J = 15.8 Hz, 1H), 4.66 (d, J = 8.9 Hz, 1H), 4.21-4.07 (m, 4H), 2.63 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) &lt;5 177.6, 176.6, 168.0, 155.3, 144.7 , 141.9, 138.4, 132.2, 128.9, 128.0, 127.8, 126.5, 124.0, 123.6, 120.9, 111.5, 109.2, 99.5, 80.1, 58.1, 43.9, 12.4 ; MS (ES+)m/z 467.9 (M+l) ° Example 11.85 6-(5-Methyl-1,2,4-11di-t--3-yl)-indole-(p-biti-2-ylindenyl)spiro[1-benzo-p-amyl-3, Synthesis of 3'-嘀哚]-2'(1Ή)-ketone

According to the procedure as described in Example 11.84, and with irrelevant changes, use 2'-keto-oxime-peptidyl-2-ylindenyl-1,2'-dihydrospiro[1-benzene And ρ 喃 _3,3,_啕哚]-6-indene nitrile replacement 4-[(Τ-keto-2,3-dihydrospiro[吱,[2,3-g][l,4 Benzodioxanthene-8 吲哚Η'(2Ή)-yl)methyl]benzonitrile to give 6-(5-methyl-1,2,4-oxadiazol-3-yl) - Γ-(pyridin-2-ylindenyl)spiro[1-benzofuran-3,3,-indole]-2'(1Ή)-one (61%) as colorless solid: mp 147-148 C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 8.57 (d, J = 4.7 Hz, 1H), 7.70-7.61 (m, 2H), 7.56 (d, J = 7.9 Hz, 1H ), 7.32-7.11 (m, 4H), 7.06-6.98 (m, 3H), 6.95-6.86 (m, 1H), 5.20 (d, J = 15.8 Hz, 1H), 5.07 (d, J = 9.1 Hz, 1H), 5.00 (d, J = 15.8 Hz, 1H), 4.79 (d, J = 9.1 Hz, 1H), 2.63 (s, 1H); 13 C NMR (75 MHz, CDC13) δ 177.0, 176.5, 168.1, 161.1, 155.4, 149.6, 142.2, 137.1, 132.2, 131.9, 129.1, 128.5, 124.0, 123.8, 123.7, 122.9, 121.7, 120.9, 109.7, 109.3, 80.0, 58.1, 46.2, 143924-sp-20091127-5 -760- 201020257 12.4 ; MS (ES+) m/z 410.9 (Μ + 1). Example 11.86 3-[(2'-keto-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxene _8,3, _ ♦)]- Synthesis of Γ(2Ή)-yl)methyl]benzoic acid

❹ Η (2'-keto-2,3_dihydrospiro [bito-[2,3-g][l,4]benzodioxanthene-8,3'-吲嗓]- 1·(2Ή)-yl)hydrazinomethyl benzoate (5.2 g, 11.73 mmol). The solution in tetrahydrofuran (150 ml) and water (80 ml) was cooled to 〇 ° C under nitrogen. Lithium hydroxide (1.13 g, 47.4 mmol) was slowly added. The reaction mixture was stirred at 0 &lt;0&gt;C for 30 min, allowed to warm to ambient temperature and then stirred for 16 hrs and concentrated in vacuo. The residue was poured into cold (??) hydrochloric acid (100 mL) to cause a precipitate to precipitate. The mixture was allowed to stand at ambient temperature for 2 hours and filtered. The solid was washed with water and hexane to give 3-[(2,-ketoindol-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene. Alkene-8,3·-蚓哚]-Γ(2Ή)-yl)indenyl]benzoic acid (5.08 g, 99%), m.p. (: (hexane); 1H NMR (300 MHz, CDC13) δ 8.03-8.00 (m, 2 Η), 7.59-7.44 (m, 2H), 7.21-7.16 (m, 2H), 7.04-7.00 (m, 1H ), 6.73-6.71 (m, 1H), 6.50 (s, 1H), 6.31 (s, 1H), 5.24-4.60 (m, 5H), 4.15-4.07 (m, 4H); 13 C NMR (75 MHz, CDC13) δ 177.7, 170.7, 155.2, 144.7, 141.7, 138.5, 136.3, 132.56, 132.3, 130.0, 129.7, 129.3, 128.9, 128.6, 124.1, 123.7, 120.9, 111.6, 109.1, 99.5, 80.0. 64.5.63.9.58.1 , 43.6 ; MS (ES+) m/z 429.7 (M + 1). 143924-sp-20091127-5 -761 · 201020257 Example 11.87 4-[(2'-keto-2,3-dihydrospiro[吱And OgHM] benzodioxanthene _8,3,_ W嗓]-Γ(2Ή)-yl) fluorenyl; 1 benzoic acid synthesis

Follow the procedure as described in Example 11.12, and perform irrelevant changes using 4-[(2'-keto-2,3-dihydrospiro[2,3-g][l,4 Methyl benzodioxanthene-8,3'-蚓哚]-indole (2Ή)-yl)methyl]benzoate was substituted for 3_[(2,-keto- 5,6-dihydrospiro) [Benzo[l,2-b: 5,4-1)'] two bites "South-3,3'-吲嗓]-Γ(2Ή)-yl)indolyl]methyl benzoate' obtained 4- [(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,3·-θbdu]-1 '(2Ή)-yl) fluorenyl]benzoic acid (89%) as a colorless solid: m.p. 234-237°C (water); 1H NMR (300 MHz, CDC13) &lt;5 12.94 (s, 1 Η), 7.93-7.86 (m, 2H), 7.46-7.40 (m, 2H), 7.26-7.19 (m, 1H), 7.18-7.13 (m, 1H), 7.04-6.92 (m, 2H), 6.50 (s, 1H) ), 6.12 (s, 1H), 5.07-4.90 (m, 2H), 4.80 (d, J = 9.3 Hz, 1H), 4.65 (d, J = 9.3 Hz, 1H), 4.19-4.03 (m, 4H) 13C NMR (75 MHz, CDC13) δ 177.3, 167.5, 155.2, 144.7, 142.6, 141.9, 138.3, 132.1, 130.5, 130.2, 129.3, 127.8, 124.2, 123.7, 121.6, 111.6, 109.8, 99.3, 79.9, 64.7, 64.1, 57.7, 43.4; MS (ES+) m/z 429.9 (M + 1) 〇Example 11 .88 Γ-[(4-methylhexahydropyrrol-1-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b·]difuran- Synthesis of 3,3'-啕哚]-2'(1Ή)-ketohydrochloride 143924-sp-20091127-5 -762- 201020257

5,6-one wind snail [本和[l,2-b . 5,4-b'] two bite 嗔-3,3'-4丨嗓] (0.35 g, 1.2 mmol), N- A mixture of methylhexahydropyrazine (1.4 ml, u mmol), 37% w/w aqueous formaldehyde (1.0 mL, 11 mmol) and methanol (2 mL) was heated for 2 h. The reaction mixture was poured into water (1 mL) to cause precipitation of _ precipitate. The solid was collected by filtration and dissolved in di-methane. The resulting solution was filtered with a sulfuric acid lock dehydration and concentrated in vacuo. The residue was dissolved in dry MeOH (2 mL) and EtOAc (EtOAc) The reaction mixture was diluted with a riddle (2 mL) and the solid was collected by filtration and washed with diethyl ether (2 X 10 mL) to give decyl hexahydrop to -1--1-yl)methyl]-5 ,6-Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-indole]-2'(1Ή)-one hydrochloride (0.38 g, 65 %), as a colorless solid: mp 181 ° C (decomposition) (diethyl ether); iHNMROOOMHz 'CDCDSllM 〇 (br s, 1H), 7.37-7.24 (m, 2H), 7.16-7.11 (m, 1H), 7.08-7.00 (m, 1H), 6.71 (s, 1H), 6.36 (s, 1H), 5.99 (br s, 4H), 4.82-4.58 (m, 4H), 4.45 (t, J = 8.7 Hz, 2H), 3.45 -2.73 (m, 10H), 2.67 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 179.1, 161.6, 161.0, 143.3, 132.5, 129.0, 124.0, 123.8, 120.8, 120.6, 120.0, 110.6, 92.8, 80.6, 72.6, 60.7, 57.4, 52.0, 47.2, 47.1, 42.3, 28.9, 11.9; MS (ES+) m/z 392.0 (M + 1). Analytics calculated for C23H25N303 · 2.5HC1: C, 57.24; H, 5.74; N, 8.71. Found: C, 57.23; H, 5.66; N, 8.34. Example 11.89 Ν'-Hydroxy-2-(2-keto-2,3-dihydrospiro[1,3-g][l,4]benzodioxanthene 143924-sp-20091127- 5 -763· 201020257 Synthesis of ene-8,3'-throate]-1·(2Ή)-yl) acetimimine

According to the procedure as described in Example 11.82, and with irrelevant changes, (2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzo Dioxin ortho-salt-8J-吲哚]-1'(2Ή)-yl)acetonitrile replacement 3-[(2'-keto-2,3-dihydrospiro[吱2南[2,3-g] ][l,4]benzodioxanthene-8,3'-啕哚]-Γ(2Ή)-yl)indenyl]benzonitrile, obtaining Ν'-hydroxy-2-(2'-one Base-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-啕哚]-1'(2Ή)-yl) Ethylamine (75%) is a colorless solid: MS (ES+) m/z 367.9 (M+l). Example 11.90 1 _{[5-(difluoromethyl)-1,2,4 -11 depletion dioxin-3-yl] fluorenyl}-2,3-dihydrospiro[? Fuming and [2,3-g][l,4]benzodioxanthene-8,3 ·-啕哚]-2'(1Ή)-ketone synthesis

According to the procedure as described in Example 11.27, and with irrelevant changes, use Ν·-radio- 2-(2,-keto-2,3-dihydrospiro[吱,[2,3-g] ][l,4]benzodioxanthene-8,3'-吲哚]_ι'(2Ή)-yl)acetamidamine amine substitution Ν'-hydroxyl-keto-5,6 -Dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3,-throindole-1,(2Ή)-yl)methyl]benzoxanthene Amine, obtained Γ-{[5-(trifluoromethyl)-1,2,4-oxadiazole each 143924^sp-20091127-5 -764. 201020257 base]methyl}-2,3-dihydrospiro [pf-[2,3-g][l,4]benzodioxanthene-8,3'-W 哚]-2'(1Ή)-one (55%) as a colorless solid: Melting point 159-160 ° C (diethyl ether); β NMR (300 MHz, CDC13) δ 7.31-7.23 (m, 1 Η), Ί.22-1. Π (m, 1 Η), 7.12-7.04 (m, 1H), 6.85 (d, J = 7.8 Hz, 1H), 6.48 (s, 1H), 6.33 (s, 1H), 5.27 (d, J = 16.8 Hz, 1H), 5.08 (d, J = 16.8 Hz, 1H), 4.92 (d, J = 9.0 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.21-4.07 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.3, 167.0, 155.2, 144.8, 140.7, 138.4, 132.2, 129.0, 124.3, 124.2, 120.7, 115.7 (q, J = 274.0 Hz), 111.9, 108.5, 99.4, 79.9, 64.5, 63.9, 58.0, 35.6; MS (ES+) m/z ❹ 445.9 (M+1). Example 11.91 2-(2'-keto-2,3-dihydrospiro[pfrano[2,3-g][l,4]benzodioxanthene]-1' (2Ή) -base) synthesis of acetamidine

(2-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene]-1'(2Ή)-yl) Ethyl ester (ο% gram, 〇92 mmol) was added to a solution of hydrazine (0.15 mL, 184 mmol) in ethanol (1 mL) and the solution was heated under reflux for 16 hours. When it is allowed to cool to ambient temperature, a solid precipitate forms. The solid was filtered and washed with ethanol (2 mL) to give 2-(2'-keto-2'3-dihydrospiro[furo[2,3_g][1,4]benzodioxanthene _8,3,-吲哚]-Γ(2'Η)-yl)acetamidine (0.285 g, 84%), as colorless solid: MS (es+) m/z 367.9 (Μ + 1) 〇143924 -sp-20091127-5 -765· 201020257 Example 11.92 1'-{[5-(Trifluoromethyl)·13,44 oxadiazolyl]methyl}_2 3 dihydrospiro[味喃[2'3- g][l'4] Synthesis of benzodioxanthene _8, κ哚]_2·(1Ή) ketone

2-(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-&lt;· bow丨哚H'(2'H)-yl)acetamidine (0.21 g, 0.57 mmol) in a solution of pyridine (3 mL), at 〇 ° C, added trifluoroacetic anhydride ( The solution was stirred at ambient temperature for 1 hour, poured into 1M hydrochloric acid (25 mL), and the mixture was extracted with ethyl acetate (3 χ 5 mM). The combined organic extracts were washed with brine (1 X 50 mL The residue was purified by column chromatography and eluted with ethyl acetate ethyl acetate in 10% to 50% gradient of hexanes, then recrystallized from diethyl ether to give 1,-{[5-(trifluoromethyl) -1,3,4-oxadiazol-2-yl]fluorenyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3,-吲哚]-2,(1Ή)-ketone·(0.05 g, 18%), as pale yellow solid: s. (: (ether); 1H NMR (300 MHz, CDC13) δ 7.34-7.17 (m, 2H), 7.14-7.07 (m, 1H), 6.94 (d, J = 7.9

Hz, 1H), 6.49 (s, 1H), 6.24 (s, 1H), 5.36-5.17 (ABq, 2H), 4.91 (d, J = 9.06 Hz, 1H), 4.66 (d, J = 9.1 Hz, 1H ), 4.21-4.07 (m, 4H) ; 13C NMR (75 MHz, CDCI3) δ 177.2, 163.4, 155.2, 144.9, 140.3, 138.5, 131.8, 129.2, 124.5, 124.4, 120.3, 111.6, 108.5, 99.5, 79.9, 64.6, 63.9, 58.0, 34.8; MS (ES+) m/z 445.9 (M + 1). 143924-sp-20091127-5 -766- (S) 201020257 Example 11.93 Γ-(3-Aminobenzyl)-2,3-dihydrospiro[吱,[2,3-g][l,4] Synthesis of benzodioxanthene-8,3·-吲哚]-2'(1·Η)-one

Γ Γ-(3-Nitrobenzyl)-2,3-dihydrospiro[pufrano[2,3-g][l,4]benzodioxene-8,3'-吲哚]-2'(1Ή)-ketone (2.7 g, 6.3 mmol), hydrazine hydrate (2.5 g, 50 mmol) and 阮nilu (〇.1 g) in decyl alcohol (5 ml) The suspension was stirred at ambient temperature under nitrogen for 16 hours. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The recrystallization of the residue from gas/hexane (1/1, 20 mL) gave Γ-(3-aminobenzyl)-2,3-dihydrospiro[2,3-g ][l,4]benzodioxanthene-8,3'-throindole-2'(1Ή)-_ (1.93 g, 76%), as colorless solid: MS (ES+) m/z 400.9 (Μ + 1). ❹ Example 11.94 N-{3-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3 Synthesis of '-啕哚Η'(2Ή)-yl) fluorenyl]phenyl}decanesulfonamide

In a 50 ml round bottom flask, Γ-(3-aminomercapto)_2,3-dihydrospiro[吱143924-sp-20091127-5 -767- 201020257 0Nan[2,3-g][ l,4] Benzodioxanthene _8,3'-p 丨p朵]_2, (ι'η) ketone (0.4 g, 1 〇 millimol), &gt;» ratio 0 (0.16 Gram '2.0 millimoles' and two gas simmer (1 〇 ml). A solution of chlorinated methane (0.115 g, 1. 〇 mmol) in dioxin (5 ml) was added at 5 C. The reaction mixture was allowed to warm to ambient temperature and stirred for 16 hours. The reaction mixture was diluted with methylene chloride (50 mL) andEtOAcEtOAc The organic phase was dehydrated and dried by filtration of citric acid and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate in dichloromethane from 〇% to 〇〇% to give N-{3-[(2'- yl-2,3- Dihydrospiro[p-flavored [2,3-g][l,4]benzodioxolene _ -8,3·-蚓哚]-1'(2Ή)-yl) fluorenyl]benzene Methanesulfonamide (0.39 g, 82%), as an off-white solid: 4 NMR (300 MHz, DMSO-d6) &lt;5 9.81 (s, 1 Η), 7.32-6.90 (m, 8H), 6.49 (s , 1H), 6.18 (s, 1H), 4.89 (ABq, 2H), 4.71 (,2H), 4.18-4.04 (m, 4H), 2.90 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6 ) δ 177.2, 155.2, 144.6, 142.7, 139.3, 138.3, 138.0, 132.0, 130.1, 129.2, 124.1, 123.5, 122.8, 121.4, 118.7, 117.9, 111.7, 109.9, 99.2, 80.0, 64.6, 64.0, 57.7, 43.3; MS (ES+) m/z 478.9 (M + 1).

Example 11.95 -[(1-Oxylpyridin-2-yl)methyl]-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8 Synthesis of 3'-吲哚]-(1Ή)-ketone

1'-7-pyridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxane 143924-sp-20091127-5 -768 · (8) 201020257 urethane-8,3'-4哚]-2'(1·Η)-ketone (0.39 g, io millimolar) and 3_gas-based benzoic acid (60% w/w, A solution of 0.43 g, 1.5 mmoles in di-methane (2 mL) was stirred at ambient temperature for 16 h. The reaction mixture was diluted with EtOAc (EtOAc)EtOAc. The organic phase was dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography and eluted with 5% to 10% gradient of decyl alcohol in dioxane to give 14 (1 - oxidized pyridin-2-yl)methyl]_2,3_ Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3Lp?丨哚]_2, (1Ή), ® (0.23 g, 57%), Off-white solid: 4 NMR (300 MHz, DMSO_d6) δ 8.31-8.26 (m, 1 Η), 7.30-6.94 (m, 7H), 6.48 (s, 1H), 6.23 (s, 1H), 5.24 (, 2H), 4.78 (ABq, 2H), 4.20-4.06 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) δ 177.9, 155.3, 146.0, 144.7, 141.6, 139.8, 138.3, 131.8, 129.2, 125.8, 124.9, 124.4, 124.0, 123.9, 120.6, 111.4, 109.4, 99.5, 80.2, 64.5, 63.9, 58.1, 39.1; MS (ES+) m/z 402.8 (M + 1) 〇 Example 11.96 2-[(2'-keto- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-H丨嗓]-1'(2Ή)-yl)曱Base]p ratio bite_3-slow acid synthesis

In a 250 ml round bottom flask, packed with 2-[(2'-keto-2,3-dihydrospiro[吱2,3-g][l,4]benzodioxanthene) -8,3'-吲哚]-ΐ, (2Ή)-yl)methyl]pyridine-3-carboxylic acid ethyl ester (2.3 g, 5.0 mmol), lithium hydroxide (0.48 g, 20.0 mmol) ),

143924-sp-20091127-5 -769- 201020257 Tetrahydrofuran (30 ml), water (50 ml) and methanol (3 ml). The reaction mixture was stirred under nitrogen and reflux for 5 hrs, cooled to ambient temperature and concentrated in vacuo. The residue was dissolved in water (1 mL) and acidified to pH 1 by the addition of 10M hydrochloric acid. The solid was collected by filtration, washed with water and recrystallized from ethanol (50 ml) to give 2 [(2, keto-2,3-dihydrospiro[[in][23_g][l,4] benzodiazepine Oxygen decene _8,3,-,5丨哚]-1,(2Ή)-yl) fluorenyl] is a grayish white solid: 1 η NMR (by 1.76 g, 91%) 300 MHz (DMSO, d6) 6.49-6.44 (m5 2H), 5.39 (ABq, 2H), ® 4.72 (ABq, 2H), 4.24-4.00 (m, 4H). Example 11.97 1 -[(3-Amino p to bit-2-yl) Methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-thirsty]-2'(1Ή)- Synthesis of ketone hydrobromide

In a 50 ml round bottom flask, filled with 2-[(2,-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3'-吲哚]-1'(2Ή)-yl)fluorenyl>pyridin-3-carboxylic acid (0.86 g, 2.0 mmol), diphenyl azide (0.69 g, 2.5 m) Mole), triethylamine (0.25 g, 2.5 mmol), tri-butanol (1.48 g, 20.0 mmol) and toluene (20 mL). The reaction mixture was stirred for 3 hours under nitrogen and reflux. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (EtOAc). The organic phase was washed with water (2×50 mL) with anhydrous magnesium sulfate 143924-sp-20〇91127-5 •770·

201020257 Dehydrated and dried' filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate in EtOAc EtOAc EtOAc. The solid formed was dissolved in dichloromethane (20 mL) and a 30% w/w solution (2.4 g, 10.0 mmol) of hydrogen bromide in acetic acid was added. The reaction mixture was stirred at ambient temperature for 16 hours' and concentrated in vacuo. The residue was recrystallized three times from decyl alcohol (20 mL) to give ι _[(3_amine s. ,3-g][l,4]benzodioxanthene _8,3,_吲11 wood]-2 (ΓΗ)-_hydrobromide (0.28 g '32%)' is an off-white solid: 1 η NMR Ref (300 MHz, CDC13) δ 8.02-7.72 (m, 3H), 7.54 (dd, J = 8.5, 5.5 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.14-7.00 ( m, 2H), 6.43 (s, 1H), 6.14 (s, 1H), 5.49 (s, 2H), 4.67 (ABq, 2H), 4.17-3.98 (m, 4H) ; MS (ES+) m/z 402.0 (M + 1). For C23H2〇N304 · 1.2 HBr: C, 55.41; H, 4.08; N, 8.43; Found: C, 55.84; H, 4.36; N, 8.29. Example 11.98 N-{2-[(2'-_yl-2,3-dihydrospiro[1,3-g][l,4]benzodioxanthene should be 8,3 - Μ丨"木]-1 (2H)-yl)methyl]p than bite _3_ based on the synthesis of brewing amine

In a 50 ml round bottom flask, 'filled with ^[(3-aminopyridine-2-yl)methyl]_2,3_dihydrospiro[吱,[2,3-g][l,4]benzoic Oxygen decene _8,3, _ 吲哚 hydrogen oxalate (0.56 g, 1.0 mmol), gasified methane sulfonate (ou gram, millimolar), pyridine (0.25 g, 3,0 mmol) Ear) and dioxane (2 ml). 143924-sp-20091127-5 -771 - 201020257 The reaction mixture was stirred under nitrogen and ambient temperature for 16 h and diluted with di-methane (50 mL). The organic phase was washed with water (2 mL 5 mL), dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography and re-crystallized from ethyl acetate in a methylene chloride to a 1% gradient eluted with methanol (10 mL) to yield N_{2_[(2, -keto-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene]-Γ(2Ή&gt;yl)methylidene-3- Methanesulfonamide (〇·18 g, 38%), as an off-white solid: 1H NMR (300 MHz, DMSO-d6) &lt;5 9.64 (s, 1 Η), 8.27 (dd, J - 4.6, 1.2 Hz , 1H), 7.78 (dd, J = 8.0, 1.4 Hz, 1H), 7.34 (dd, J = 8.0, 4.7 Hz, 1H), 7.21-7.10 (m, 2H), 6.96 (t, J = 7.4 Hz, 1H), 6.77 (d, J = 7.8 Hz, 1H), 6.48 (s, 1H), 6.46 (s, 1H), 5.17 (ABq, 2H), 4.73 (ABq, 2H), 4.18-4.05 (m, 4H ), 3.14 (s, 3H); 13 C NMR (75 MHz, DMSO-d6) 5 177.6, 154.9, 151.0, 147.1, 144.5, 143.2, 138.1, 134.5, 132.6, 132.2, 132.1, 129.0, 123.8, 123.2, 122.2 , 112.3, 109.4, 99.0, 79.6, 64.6, 64.1, 57.8, 41.8, 40.6; MS (ES+) m/z 479.9 (M + 1). Example 11.99 Γ-(hexahydropyridin-4-ylindenyl)-2 ,3-dihydrospiro[,,[2,3-g][l,4]benzodioxolene-8,3M丨哚]-2'(1Ή)-one hydrochloride Synthesis

4-[(2,-keto-2,3-dihydrospich-[HgK1,4]benzodioxanthene-8,3,-呻嗓]-1'(2Ή)- ))methyl]hexahydro 17 is a solution of tert-butyl acid tert-butyl ester (4.10 g ' 9.53 mmol) in methanol (1 mL). Add 2 oxime ether etherification 143924-sp-20091127- 5 • 772- 201020257 Hydrogen (20 ml '40 mmol). The mixture was stirred at ambient temperature for 5 hours and concentrated in vacuo. The residue was triturated in diethyl ether (5 mL) to give bis-(hexahydropyridin-4-ylmethyl)-2,3-dihydrospiro[2,3-g][l, 4] Benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one hydrochloride (3.50 g, 86%): 4 NMR (300 MHz, DMSO-d6) 5 9.06- 8.50 (br s, 2H), 7.39-7.31 (m, 1H), 7.22-7.02 (m, 3H), 6.51 (s, 1H), 6.19 (s, 1H), 4.73 (d, J = 9.3 Hz, 1H ), 4.61 (d, J = 9.3 Hz, 1H), 4.23-4.06 (m, 4H), 3.73-3.52 (m, 2H), 3.31-3.19 (m, 2H), 2.92-2.70 (m, 2H), 2.16-2.00 (m, 1H), 1.87-1.71 (m, 2H), 1.52-1.30 (m, 2H); MS (ES+) m/z ❹ 393.0 (M + 1). Example 11.100 1'-{[1-(1-Mercaptoethyl)hexahydropyridin-4-yl]indolyl}-2,3-dihydrospiro[吱,[2,3-幻[1,4 Synthesis of benzodioxanthene _8,3,_啕哚]_2,(1Ή)·ketohydrochloride

添加 Add 1'-(hexahydropyridyl-4-ylmethyl)_2,3- in a mixture of acetone (0.19 ml, 2.5 mmol) and 1,2-dichloroethane (5. Dihydrospiro-I; oxime-[2,3-g][l,4] benzodioxanthene _8,3'_吲嗓]-2'(1Ή)-ketohydrochloride (0.36 g) , 0.84 mmol, triethylamine (ο.% mL, 25 mmol) and triethyloxyborohydride (0.534 g, 2.52 mmol). The mixture was stirred at ambient temperature for 16 hours, and concentrated in vacuo. EtOAc m. And methylethyl)hexahydropyridyl]methyl}_2,3_dihydrospiro [biting and illusion] benzodioxanthene-8,3'-吲哚]-2' (1Ή)-ketone. To a solution of this compound in methanol 143924-sp-20091127-5-773-201020257 (5 ml), a 4M solution of hydrogen chloride in 1,4-dioxane (1.0 ml '4.0 mmol) was added. The mixture was stirred at ambient temperature for 3 minutes and concentrated in vacuo. The residue was successively developed in hexane and B to obtain Γ-{ [1-(1-methylethyl) hexahydrop than butyl-4-yl]methyl b 2,3-dihydrospiro[p Shout and [2,3-g][l,4]benzodioxanthene -8,3'-indole]-2'(1Ή)-ketohydrochloride (0.21 g, 53%), It is an off-white solid: m.p. 213-216°C; iHNMR (300MHz, DMSO dg) δ 10.02-9.80 (br s, 1H), 7.40-7.02 (m, 4H), 6.51 (s, 1H), 6.18 (s, 1H) ), 4.74 (d, J = 9.3 Hz, 1H), 4.62 (d, J = 9.3 Hz, 1H), 4.23-4.06 (m, 4H), 3.73-3.21 (m, 4H), 3.00-2.78 (m, 2H), 2.20-1.52 (m, 5H), 1.32-1.12 (m, 7H); 13 C NMR (75 MHz, DMSO-d6) δ 176.8, 154.7, 144.0, 142.5, 137.7, 131.6, 128.7, 123.5, 122.8 , 121.0, 111.1, 109.2, 98.6, 79.7, 64.1, 63.5, 57.1, 56.7, 47.1, 44.2, 32·1, 26.6, 26.4, 16.1; MS (ES+) m/z 435.1 (M+l). Example 11.101 r-[(l-Methylhexahydropyridin-4-yl)indolyl]-2,3-dihydrospiro[B-pyrano[2,3-g][l,4]benzodioxan Synthesis of terpene-8,3'-吲哚]-2'(1Ή)-keto hydrochloride

According to the procedure described in Example 11.100, and irrelevant changes were made, the acetone was replaced with 37% w/w aqueous formaldehyde solution, and the tetrachlorofuran was replaced with tetrahydrofuran to obtain hydrazine-[(1-methylhexahydropyridine). )methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3,_(9)哚]_2, (l,H) - ketohydrochloride (60%), m.p. 6.46 (s, 1H), 6.15 (s, 1H), 143924-sp «20091127-5 -774- 201020257 4.80-4.50 (m, 2H), 4.25-4.00 (m, 4H), 3.74-2.50 (m , 9H), 2.10-1.38 (m, 5H); MS (ES+) m/z 407.1 (M + 1). Example 11.102 1'-(Hofopin-2-ylindenyl)-2,3-dihydrospiro[,,[2,3-g][l,4]benzodioxanthene-8 ,3'-chao哚]-2'(1Ή)-ketone synthesis

Φ In the Parr bottle, l'-[(4-mercapto-oxalin-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene-8,3'-(tetra)anthracene-2'(1Ή)-one (3.36 g, 6.93 mmol) suspended in methanol (20 ml) and ethyl acetate (20 ml) In, and add /竣 (20% w/w, 0.50 g). The mixture was shaken in a Parr hydrogenation apparatus at 50 psi and at ambient temperature for 16 hours. The reaction mixture was filtered through a pad of celite pad and filtrate was concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate / methanol / 7N methanolic ammonia (10:1:0.1) to afford 1'- (hofolin-2-ylindenyl)- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3W丨哚]-2'(1Ή)-one (1.7 g, 62 %), as a colorless foam: mp 154-159 ° C; NMR (mixture of diastereomers, 3 〇〇 MHz, CDC13) δ 7.33-7.24 (m, 1H), 7.17-7.00 (m, 3H), 6.49 (s, 0.5H), 6.48 (s, 0.5H), 6.24 (s, 0.5H), 6.21 (s, 0.5H), 4.91-4.85 (m, 1H), 4.66-4.60 (m, 1H), 4.22-4.08 (m, 4H), 3.94-3.51 (m, 5H), 3.00-2.61 (m, 4H); MS (ES+) m/z 395.1 (M + 1). Example 11.103 Γ-{ [4-(1-methylethyl)norfolin-2-yl]methyl b 2,3-dihydrospiro [cough and 143924-sp-20091127-5-775-201020257 [ 2,3-g][l,4]benzodioxanthene_8,3,_4哚]_2, (1Ή), the synthesis

V Γ-(morpholine-2-ylindenyl)-2,3-dihydrospiro[吱,[2,3-g] was used according to the procedure described in Example 11.100, and the insignificant changes were made. [l,4]benzodioxanthene-8J-吲哚]-2'(1Ή)-ketone replacement 1,-(hexahydropyridin-4-ylindenyl)-2,3-dihydrospiro[吱 并[2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-2,(1Ή)-deanone, obtain 1'-{[4-( 1-methylethyl)fosfolin-2-yl]fluorenyl}-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene- 8,3'-thirty 哚] (88%), as colorless solid: m.p.: 102-125 ° C; iHNMR (mixture of diastereomers, 300 MHz, CDC13) δ 7.33-7.26 (m, 1H), 7.20-7.00 (m, 3H), 6.49 (s, 0.5H), 6.48 (s, 0.5H), 6.26 (s, 0.5H), 6.20 (s, 0.5H), 4.88 (d, J = 9.0 Hz, 1H), 4.67-4.61 (m, 1H), 4.21-4.07 (m, 4H), 4.00-3.56 (m, 5H), 2.85-2.56 (m, 3H), 2.35-2.05 (m, 2H), 1.02 ( d, J = 6.6 Hz, 6H) ; MS (ES+) m/z 437.2 (M + 1) ° 实例 Example 11.104 Γ-[(4-Methylmorpholin-2-yl)methyl]-2,3 Synthesis of dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-纼哚]-2'(1Ή)-one

According to the procedure described in Example 11.100 and the insignificant changes were made, -776- 143924-sp-20091127-5 (S) 201020257 The acetone was replaced with 37% w/w aqueous formaldehyde solution, and the tetrachlorofuran was replaced with tetrahydrofuran. Using 1'-(morpholin-2-ylmethyl)_2,3-dihydrospiro[吱,[2,3-g][1'4]benzodioxolene-8,3, _峋哚]_2, (1Ή)-ketone replacement 丨, (hexahydropyridyl) hydrazino-2,3-dihydrospiro[吱,[2,3_g][14]benzodioxanthene _8,3,吲嗓]-2'(1Ή)-嗣' obtained Γ_[(4_indolyl porphyrin-2-yl)methyl]_2,3 dihydrospiro[吱°南和[2, 3-g][l,4]benzodioxanthene oxime] oxime)-one (91%), as a colorless solid: m.p.: 2-1-12 ° C; 1HNMR (diastereomers) Mixture, 300 MHz, CDC13) δ 7.33-7.26 (m, 1H), 7.17-7.00 (m, 3H), 6.48 (s, 1H), 6.26 (s, 0.5H), 6.21 (s&gt; 0.5H), 4.91 -4.85 (m, 1H), 4.66-4.60 (m, 1H), 4.22-4.08 (m, 4H), 3.94-3.58 (m, 5H), 2.77 (d, J = 11.7 Hz, 1H), 2.61 (d , J = 11.7 Hz, 1H), 2.28 (s, 3H), 2.18-2.06 (m, 1H), 1.99-1.89 (m, 1H); MS (ES+) m/z 409.2 (M+ 1). Example 11.105 (8S)-1 '-[(2S)-Nalfolin-2-ylmethyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]Benzene Synthesis of Dioxinol-8,3'-吲哚]-2,(1Ή)-ketone

Using (8S)-r-{[(2S)-4-indolyl oxafolin-2-yl]methyl b 2,3-dihydrospiro[吱,[2,3-g][l,4 Benzenedioxene terpene-8J-吲哚]-2'(1Ή)-one substituted Γ-[(4-benzylmorpholine-2-yl)methyl]-2,3-dihydrospiro [Bist and [2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-2·(1Ή)-one, (8S)-1'-[ (2S)-morpholin-2-ylmethyl]-2,3-dihydrospiro[啥,[2,3-g][l,4]benzodioxene _8,3· -啕哚]-2'(1Ή)-ketone 143924-sp-20091127^5 •777- 201020257 (56%) : MS (ES+) m/z 395.1 (Μ + 1). Example 11.106 (8S)-r-{[(2S)-4-Methylmorpholine-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-笆][1 , 4] benzodioxanthene _8,3,_吲嗓]_2, (1) ketone synthesis

Following the procedure described in Example 11.100, and subject to insignificant changes, the acetone was replaced with 37% w/w aqueous formaldehyde, u-dichloroethane was replaced with tetrahydrofuran, and (83)-1,-[(25)- was used. Morpholine-2-ylmethyl]-2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxanthene]-2'(1Ή) -嗣 Replacement of ι,_(hexahydropyridin-4-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8 ,34哚]-2'(rH)-ketohydrochloride, (8S)-l,-{[(2S)-4-methylmorpholine-2-yl]indenyl}-2,3- Dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3|_ 吲哚]-2'(1Ή)-one (68%), colorless Solid: melting point 85-90. (: ; 1H NMR (300 MHz, CDC13) δ 1.21 (d, J = 7.5 Hz, 1H), 7.15-6.98 (m, 3H), 6.47 (s, 1H), 6.20 (s, 1H), 4.86 (d , J = 9.0 Hz, 1H), 4.61 (d, J = 9.0 Hz, 1H), 4.19-4.05 (m, 4H), 3.92-3.56 (m, 5H), 2.76 (d, J = 11.4 Hz, 1H) , 2.60 (d, J = 11.4 Hz, 1H), 2.26 (s, 3H), 2.17-2.05 (m, 1H), 1.97-1.87 (m, 1H) ; 13C NMR (300 MHz, CDCI3) δ 177.6, 155.1 , 144.5, 142.6, 138.2, 132.0, 128.7, 123.6, 123.2, 121.0, 111.4, 109.4, 99.2, 80.0, 73.5, 66.7, 64.4, 63.8, 58.1, 57.8, 54.6, 463, 43.1; MS (ES+) m/z 409.2 (M + 1). Example 11.107 143924-sp-20091127-5 -778· 201020257 1 -{[3-(Difluoroindolyl)p than bite_2_yl]methylpyrrolpyrano-diazole- Synthesis of 8,3'-吲哚]-2,(1Ή)-ketone

In a cooled (〇.〇) solution in di-methane (10 ml) in 3-difluoromethyl-ρ-but-2-yl) sterol hydrochloride (0.24 g, 1.1 mmol) , adding hydrazine, dimethyl carbamide (2 drops, catalytic amount) and sulfoxide (0.15 ml). The solution was stirred at ambient temperature for 16 hours and concentrated in vacuo. The residue was bathed in hydrazine, hydrazine-dimercaptoamine (1 liter ml), and added with carbonic acid (〇98 g, 3·〇 mmol), potassium iodide (1 〇〇 mg) and snail [bite喃 卩 丄 ^ like 丄 benzopyrene 嗤-8,3 '-吲哚]-2' (1 Ή)-ketone (0.28 g '1.0 mmol). The reaction was heated at 6 ° C for 3 hours, allowed to cool to ambient temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified eluting eluting eluting eluting eluting Pyridin-2-yl]methyl} sulphate[3,2-e][2,l,3]benzo- 2 嗤-8,3,-4 卜 朵]-2, (1Ή )-ketone (0.28 g '64%) as colorless solid: m.p.: 212-215°C; iHNMRQOO MHz, CDC13) δ 8.62 (d, J = 4.8 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H ), 7.82 (dd, J = 9.6, 0.9 Hz, 1H), 7.34-7.27 (m, 2H), 7.23-7.16 (m, 2H), 7.01 (dd, J = 7.5, 7.5 Hz, 1H), 6.71 ( d, J = 7.8 Hz, 1H), 5.46 (d, J = 17.4 Hz, 1H), 5.30 (d, J = 9.3 Hz, 1H), 5.21 (d, J = 17.4 Hz, 1H), 5.01 (d, J = 9.3 Hz, 1H) ; 13 C NMR (75 MHz, CDCI3) δ 176.9, 163.2, 152.5, 152.2, 148.4, 145.0, 142.8, 134.1 (q, J = 5.2 Hz), 129.8, 129.6, 125.6, 124.5, 124.1, 123.7, 123.4, 122.1, 121.9, 143924-sp-20091127-5 -779· 201020257 121.8, 119.3, 82.4, 57.3, 42.7 (q, J = 3.3 Hz) ; MS (ES+) m/z 439.1 (M + 1) 〇Example 11.108 6-Gasyl-l'-{[3-(Trifluoromethyl)acridin-2-yl]indolyl}-2,3-dihydrospiro [ Pyrano [3,2-f] [l, 4] benzo-dioxane alkenyl -9,3W Shu indol] -2 · (1Ή) - one Synthesis of

According to the procedure described in Example 11.107, and with irrelevant changes, use 6-alkyl-2,3-dihydrospiro [bito-and-[3,2-f][l,4]benzodioxime Terpene _9,3,_(f)哚]-2'(ΓΗ)-ketone-substituted snail [吱,[3,2-矹2,1,3]benzoxadiazole_8,3,-qiao ]-2'(1Ή&gt;嗣, obtaining 6_gas-based seven old ·(trifluoromethyl)pyridine_2-yl]methyl b 2,3-dihydrospiro[吱,[3,2_η[ΐ, 4] benzodioxanthene _9,3'-throindole-2, (oxime)-ketone (70%), colorless solid: melting point 273-275 ° C; 4 NMR (300 ΜΗζ, DMSO- D6) (5 8.70 (d, J = 4.5 Hz, 1H), 8.26-8.21 (m, 1H), 7.58-7.51 (m, 1H), 7.26-7.18 (m, 2H), 7.08-6.98 (m, 1H) ), 6.94-6.88 (m, 2H), 5.24 (ABq, 2H), 4.79 (ABq, 2H), 4.14-3.96 (m, 4H) ί MS (ES+) m/z 489.2 (M + 1), 491.2 ( M + 1). Example 11.109 1'-{[3-(Trifluoromethyl)P-pyridyl-2-yl]methyl}-2,3-dihydrospiro[吱,[3,2-f] [l,4] Synthesis of benzodioxanthene-9,3'-吲哚]-2'(1Ή)-one 143924-sp-20091127-5 .780· , 0 201020257

According to the procedure described in Example 11.107, and with irrelevant changes, use 2,3-dihydrospiro[吱和dioxolene-9,3,_吲哚]_ 2'(1Ή)- Ketone-substituted succinium [υϋυ]benzoxadiazole _8,3,吲哚]_ 2'(1Ή)-one, obtaining 1'-{[3-(trifluoromethyl),bipyridine 2_基]methyl b 2,3_dihydrospiro[吱,[3,2-f][l,4]benzodioxene _9 3._...哚]_2, (1Ή) , (7〇%), as a colorless solid: melting point 245-247 ° C; iHNMRGOOMHz 'CDCD^SjS^J: 4.5 Hz, 1H), 7.98 (d, J = 4.5 Hz, 1H), 7.34-7.26 (m, 1H), 7.20-7.12 (m, 2H), 7.04-6.97 (m, 1H), 6.74 (d, J = 8.7 Hz, 1H), 6.63-6.58 (m, 1H), 6.46 (d, J = 8.7 Hz , 1H), 5.56 (d, J = 17.4 Hz, 1H), 5.06 (d, J = 16.8 Hz, 1H), 4.97 (d, J = 8.7 Hz, 1H), 4.70 (d, J = 8.7 Hz, 1H ), 4.17-3.92 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 177.4, 156.2, 152.9, 152.4, 152.3, 142.3, 140.0, 138.6, ❹ 138.1, 134.1 (q, J = 5.3 Hz), 131.7 , 128.3, 124.5, 123.5, 122.9, 122.0, 118.0, 115.6, 108.4, 102.2, 81.8, 64.7, 63.9, 57.2, 42.6 (q, J = 3.1 Hz) ; MS (ES+) m/z 455.2 (M + 1)Example 11.110 1·-{[5-(Difluoroindolyl)pyran-2-yl]methyl}-2,3-dihydrospiro [Nitrate and C2,3-g][l,4] Benzo Synthesis of Dioxetine-8,3'-峋哚]-2'(1Ή)-one 143924-SD-20091127-5 -781· 201020257

According to the procedure described in Example 11.107, and with irrelevant changes, use 2,3-diaza snail [Miso-[2,3_§][1,4] benzodioxanthene _8,3 ,_吲哚]_ 2'(1Ή)-ketone replacement snail [味喃[3 2_e][2,13]benzopyrene s8_, 啕哚]_ 2'(1Ή)- brewing]' And using (5-(difluoroindolyl)pyran-2-yl)nonanol to replace 3trifluoromethyl-pyridin-2-yl)methanol hydrochloride 'to obtain the old--(difluoroindolyl)furan_ 2_yl] fluorenyl}-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxene _8,3Lp 丨嗓]-2'(1Ή) -ketone (35%) ' is a colorless solid: melting point 173_i75 ° C; WNMR (300 MHz, CDC13) δ 7.33-7.25 (m, 1H), 7.21-7.14 (m, 1H), 7.11-6.96 (m, 2H ), 6.63-6.58 (m, 1H), 6.57 (t, JH.F= 54.3 Hz, 1H), 6.50 (s, 1H), 6.37-6.34 (m, 1H), 6.20 (s, 1H), 5.04 ( d, J = 16.2 Hz, 1H), 4.94-4.83 (m, 2H), 4.65 (d, J = 9.0 Hz, 1H), 4.23-4.07 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 111 Λ, 155.2, 151.1 (t, JC.F = 2.2 Hz), 146.5, 144.6, 141.5, 138.3, 132.1, 128.9, 123.9, 123.7, 120.8, 111.5, 111.3 (t, JC.F = 4.1 Hz), 109.2, 108.9, 108.2 (t , Jc. F = 233.6 Hz), 99.4, 80.0, 64.5, 63.9, 57.9, 37.0; MS (ES+) m/z 425.9 (M + 1). Example 11.111 5,6-Difluoro-indole-(hexahydropyridin-4-ylmethyl)spiro[1-benzofuran-3,3'-indole]-2'(1Ή)-one hydrochloride Synthesis 143924-sp.20091127-5 •782- 201020257

4-[(5,6-H-2'-oxaspiro[1-benzo-p-flavor_3,3'-p!|p-]-ΐ'(2Ή)-yl)methyl] Hydrogen pyridine-1-carboxylic acid tert-butyl ester (0.47 g, 1.01 mmol) in a solution of anhydrous methanol (8 mL) and anhydrous di-methane (3 mL) - 4.0 Μ solution (4.0 mL, 16 mmol) in dioxin, and the reaction mixture was stirred at ambient temperature for 16 h. Anhydrous diethyl ether (30 ml) ❹ } was added to the reaction mixture to cause precipitation of the precipitate. The solid formed was triturated in diethyl ether (2×30 mL) to give 5,6-difluoro-1,-(hexahydropyridinyl)spiro[1-benzofuran-3,3·-嗍哚]-2·(1Ή)-Fluor I hydrochloride (0.36 g, 88%), as a colorless solid, melting point &gt; 200 ° C; 1H NMR (300 MHz, CD3 OD) &lt;5 7.40 (ddd, J = 7.6, 7.6, 1.4 Hz, 1H), 7.24-7.12 (m, 3H), 6.92 (dd, J = 10.7, 6.4 Hz, 1H), 6.69 (dd, J = 9.5, 8.0 Hz, 1H), 4.91 ( d, J = 9.4 Hz, 1H), 4.76 (d, J = 9.4 Hz, 1H), 3.85-3.65 (m, 2H), 3.47-3.37 (m, 2H), 3.05-2.93 (m, 2H), 2.32 -2.16 (m, ❹ 1H), 2.05-1.92 (m, 2H), 1.64-1.46 (m, 2H) ; 13 C NMR (75 MHz, CD3 OD) δ 179.3, 158.7 (d, JC.F = 13.0 Hz ), 152.6 (dd, JC.F= 246.7, 14.5 Hz), 146.9 (dd, JC.F= 239.8, 14.0 Hz), 144.0, 132.7, 130.7, 125.7 (dd, Jc-F= 6.5, 3.2 Hz), 125.1, 112.9 (d, JC.F = 22.2 Hz), 110.7, 100.9 (d, JC.F = 22.7 Hz), 82.2, 59.4, 46.1, 44.8, 33.8, 27.8; MS (ES+) m/z 371.3 (M + 1). For C21H2 〇F2N202 .HC1: C, 61.99; H, 5.20; N, 6.89. Found: C, 61.73; H, 5.28; N, 7.03. Example 11.112 5,6-Difluoromethylhexahydropyridin-4-yl)indolyl]spiro[1-benzofuran-3,3'- cleavage-783- 143924-SP-20091127-5 201020257 哚]-2 ·(1Ή)-ketohydrochloride synthesis

5,6-difluoro-seven (six-by-bit bite-4_ylmercapto) snail [1-benzo-pyran--3,3,-♦-dot]_ 2,(1Ή&gt; ketone hydrochloride (0.240 g) (4) 〇 莫 )) In a solution of tetrachloromethane (5 ml), add triethylamine (0.08 ml, U8 mmol), formaldehyde (37% w/w, in water, 0.18 ml, 2.24) Milliol), sodium triethoxysulfonate (0.375 g, 1.77 mmol) and acetic acid (3 drops). The reaction mixture was stirred at ambient temperature for 3.5 h and concentrated in vacuo. (1 ml) was added to the residue and the mixture was crystallised eluted eluted eluted eluted eluted eluted Purification by column chromatography and dichlorohydrazine/methanol/hydrogen hydroxide (10/1/0.2) &gt; glutathion, to give 5,6-diox-indole-[(1-mercaptohexahydro-? Bite_4-yl)methyl]spiro[1-benzofuran·3,3,-(4)哚]-2,(1Ή)-one hydrochloride (0.205 g, 90%), as a colorless solid: melting point 162-164. (: ; 4 NMR (300 MHz, CDC13) &lt;5 7.40 (dd, J = 7.5, 7.5 Hz, 1H), 7.23-7.12 (m, 3H) , 6.92 (dd, J = 10.7, 6.4 Hz, 1H), 6.69 (dd, J = 9.4, 8.0 Hz, 1H), 4.91 (d, J = 9.4 Hz, 1H), 4.76 (d, J = 9.4 Hz, (H, 2H) -1.56 (m, 2H) ; 13 C NMR (75 MHz, CDC13) δ 179.0, 158.5 (d, JC.F = 10.3 Hz), 152.3 (d, JC.F = 247.1 Hz), 146.7 (d, JC. F = 238.3 Hz), 143.9, 132.5, 131.1, 125.4, 125.0, 113.6 (d, JC.F = 19.8 Hz), 112.3, 100.8 (d, JC.F = 22.2 Hz), 83.1, 59.0, 57.0, 56.7, 46.7, 34.0, 29.6, 29.5; MS (ES+) m/z 385.3 (M + 1). Analysis and calculation of C22H22F2N202 ·2.4Ηα 143924^ρ-2009〗127-5 -784· 201020257 Value: C, 55.99; H, 5.21; N, 5.94. Real Qi ij value: c, 55 75; H, 5 19; N, 5 97. Example 12 N-(Cyclohexylmethyl)-3-[(2·-keto-5,6-dihydrospiro[benzo[12_b: 5,4_b-furfuran-3,3·-吲嗓Η·( Synthesis of 2Ή)-yl)methyl]benzamide

3-[(2-_ yl-5,6-one snail [benzo[l,2-b: 5,4-b'] two bite" south-3,3'-mouth bow 1 ρ wood] -1 (2H)-yl)methyl]benzoic acid (2.13 g, 5.1 mmol) and n,N-dimercaptocarboxamide (0.001 ml, catalytic amount) in anhydrous dioxane (3 The suspension in 〇 ml) was treated with gasified grasshopper (4.50 ml, 5.1 mmol). The reaction mixture was stirred at ambient temperature for 3 hours. The crude product is concentrated in vacuo to give gasification of 3-((2-keto-5,6-dipho-2H-spiro[benzone-p-spin and s-n-n _3,3, _ Hydroquinone]-1 -yl)indenyl)benzamide is a pale yellow solid. Gasification of 3_((2,-fluorenyl-5,6-dihydro-2Η-spiro[benzofuro[6,5_b]furan-3,3,-dihydroindole]-Γ-yl)methyl Clumsy (0.27 g, 0.6 mmol), cycloheximide (〇17 ml, 3 mM), triethylamine (0.44 mL, 3.2 mmol) and 4 (diamine) A solution of pyridine (0.005 g, catalyzed) in anhydrous dioxane (5 mL) was stirred for 20 hours at ambient temperature under nitrogen. The reaction mixture was diluted with dioxane (1 mL) and aqueous citric acid (10 mL). The organic phase was washed with water (10 mL) EtOAc. The crude product was purified by column chromatography eluting with ethyl acetate (0% to EtOAc) 5,6-dihydrospiro[benzo[nb:5,4,7,7]difuran_3 3,_ _ 143924-sp-20091127-5 •785- 201020257 哚]-1'(2Ή)-yl)曱Benzoylamine (0.33 g, 65%) as a colorless solid: 4 NMR (300 MHz, CDC13) δ 7.80 (s, 1 Η), 7.63 (d, J = 7.4 Hz, 1H), 7.48-7.37 ( m, 2H), 7.23-7.15 (m, 2H), 7.08-7.00 (m, 1H), 6.79 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.43 (s, 1H), 6.19 -6.09 (m, 1H), 5.08 (d, J = 15.7 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.91 (d, J = 15.7 Hz, 1H), 4.72 (d, J = 9.0 Hz, 1H), 4.55 (t, J = 8.6 Hz, 2H), 3.33-3.23 (m, 2H), 3.07-2.95 (m, 2H), 1.82-1.64 (m, 5H), 1.34-1.13 (m , 4H), 1.07-0.86 (m, 2H); MS (ES+) m/z 509.0 (M + 1). Example 12.1 N-(2-Methoxyethyl)-3-[(T-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran· Synthesis of 3,3'_啕哚]-1'(2Ή)-yl)methyl]phenylamine

Following the procedure as described in Example 12, and carrying out an insignificant change, cyclohexylmethylamine was replaced with 2-methoxyethylamine to give Ν-(2-methoxyethyl)-3-[(2) '-keto-5,6-di-spiro[benzo[l,2-b: 5,4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl Benzoguanamine (67%) as a colorless solid: m.p.: 72-73 ° C (hexane / ethyl acetate); 1H NMR (300 MHz, CDC13) 5 7.83, (s, 1H), 7.65 (d, J = 6.3 Hz, 1H), 7.46-7.36 (m, 2H), 7.22-7.17 (m, 2H), 7.06-7.01 (m, 1H), 6.78 (d, J =7.7 Hz, 1H), 6.56-6.51 (m, 1H), 6.51 (s, 1H), 6.43 (s, 1H), 5.08 (d, J = 15.7 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.91 (d, J = 15.7 Hz, 1H), 4.72 (d, J = 9.0 Hz, 1H), 4.57-4.51 (m, 2H), 3.67-3.62 (m, 2H), 3.57-3.54 (m, 2H), 3.38 (s, 3H ), 3.05-2.98 (m, 2H); MS (ES+) m/z 471.0 (M + 1). Example 12.2 143924-sp-20091127-5 -786- 201020257 N-hexyl-N-mercapto-3-[(2·-keto-5,6-dihydrospiro[benzo[i,2-b: 5] Synthesis of 4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzoguanamine

Following the procedure as described in Example 12, and carrying out an insignificant change, the cyclohexylmethylamine was replaced with Ν-hexylmethylamine to obtain Ν_hexyl-Ν_methyl_3_[(2ι_ ketone-5). 6-Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3·-&lt;哚]-1'(2Ή&gt;yl)methyl]benzoguanamine 80%), as a colorless solid: m.p.: 73-74 ° C (hexane / ethyl acetate); 4 NMR (300 MHz, CDC13) d 7.41-7.36 (m, 3H), 7.31-7.26 (m, 1H), 7.22- 7.16 (m, 2H), 7.05-7.00 (m, 1H), 6.82-6.75 (m, 1H), 6.49 (s, 1H), 6.43 (s, 1H), 5.08 (d, J = 15.7 Hz, 1H) , 4.92 (d, J = 9.0 Hz, 1H), 4.86 (d, J = 15.7 Hz, 1H), 4.71 (d, J = 8.6 Hz, 1H), 4.55 (t, J = 8.6 Hz, 2H), 3.19 -3.12 (m, 1H), 3.05-2.84 (m, 5H), 1.64 (m, 2H), 1.56-1.47 (m, 1H), 1.38-1.34 (m, 3H), 1.22-1.04 (m, 3H) , 0.96-0.79 (m, 3H); MS (ES+) m/z 511.1 (M + 1). φ Example 12.3 N-(2-ethylbutyl)-3-[(2·-keto-5, 6-Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3W丨哚]-1·(2·ί^)-yl)methyl]benzamide Synthesis

Following the procedure as described in Example 12, and performing an insignificant change 'replacement of cyclohexane decylamine with 2-ethyl-n-butylamine, ν-(2-ethylbutyl)- 143924-sp was obtained. -20091127-5 •787- 201020257 3-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]difuran-3,3,- W 哚]-1,(2Ή)-yl)methyl]benzoguanamine (40%), as a colorless solid: m.p., </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; 300 MHz, CDC13) δ 7.80 (s, 1H), 7.62 (d, J = 7.3 Ηζ, 1Η), 7.47-7.38 (m, 2Η), 7.23-7.15 (m, 2Η), 7.06-7.00 (m, 1Η) ), 6.79 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.43 (s, 1H), 6.10-6.01 (m, 1H), 5.09 (d, J = 15.9 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.91 (d, J = 15.9 Hz, 1H), 4.72 (d, J = 9.0 Hz, 1H), 4.55 (t, J = 8.7 Hz, 2H), 3.44-3.38 (m, 2H), 3.05-2.96 (m, 2H), 1.55-1.46 (m, 1H), 1.42-132 (m, 4H), 0.93 (t, J = 7.3 Hz, 6H); MS (ES+) m /z 497.0 (M + 1). ❹ Example 12.4 N-(2,4-Dimercaptophenyl)-3-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b, Synthesis of difuran-3,3'-吲哚Η'(2Ή)-yl)indolyl]benzamide

According to the procedure as described in Example 12, and irrelevant changes were made, 环 2,4-diphenylaniline was substituted for cyclohexane decylamine to obtain N_(2,4-didecylphenyl)_ 3-[ (2'-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]difuran-3,3,-啕哚]-Γ(2Ή)-yl) Benzoamine phenylhydrazine (57%) as colorless solid: mp 234-235e (hexane / ethyl acetate); 1H NMR (300 MHz, CDC13) 5 7.89 (s, 1H), 7_77 (d, J = 7.6 Hz, 2H), 7.57-7.45 (m, 3H), 7.24-7.18 (m, 2H), 7.07 (s, 1H), 7.06-7.02 (m, 2H), 6.82 (d, J = 7.8 Hz, 1H), 6.47 (s, 1H), 6.43 (s, 1H), 5.19 (d, J = 15.7 Hz, 1H), 5.00 (d, J = 9.0 Hz, 1H), 4.88 (d, J = 15.7 Hz, 1H), 4.72 (d, J = 9.0 Hz,

1H), 4.53-4.35 (m, 2H), 2.91-2.84 (m, 2H), 2.31 (s, 3H), 2.20 (s, 3H) ; MS 143924-sp-20091127-5 •788· (S) 201020257 (ES+) m/z 516.1 (M+l) 〇 Example 12.5 3-[(2'-keto-5,6-dihydrospiro[benzo(10)7:5,4_b,]difuran·3,3 ,__朵朵]_Γ(2Ή)_ base) methyl propyl) benzamide synthesis

❹ Following the procedure described in Example 12, and performing irrelevant changes, replacing cyclohexanemethylamine with 2-phenylpropan-1-amine to obtain 3_[(2,·keto-5,6-dihydrogen) Snail [benzo[l,2-b: 5,4-b]difuran_3,3,-吲哚]-indole, (2Ή)-yl)methyl]-indole-(2-phenylpropyl Benzoylamine (82%) as a colorless solid. · iHNMR (300MHz, (CD3) 2CO) δ 7.88 (s, 1H), 7.83-7.73 (m, 1H), 7.70 (d, J = 7.7 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.45-7.38 (m, 1H), 7.34-7.14 (m, 7H), 7.09-7.01 (m, 1H), 6.93 (d, J = 7.8 Hz , 1H), 6.63 (s, 1H), 6.34 (s, 1H), 5.15 (d, J = 15.9 Hz, 1H), 4.94 (d, J = 9.2 Hz, 1H), 4.92 (d, J = 15.9 Hz , 1H), 4.76 (d, J = 9.1 Hz, 1H), 4.53 (t, J = 8.7 Hz, 2H), 3.58-3.50 (m, 2H), 3.19-2.93 (m, 3H), 1.28 (d , J = 7.0 Hz, 3H) ; MS (ES+) m/z 531.1 (M + 1). Example 12.6 N-[(1S)-1-cyclohexylethyl]-3-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b, Synthesis of difuran-3,3'-吲哚]-indole (2Ή)-yl)methyl]phenylamine

143924-sp-20091127-5 -789· 201020257 According to the procedure as described in Example 12, and irrelevant changes were made, using SM+H-cyclohexylethylamine in place of cyclohexane decylamine, N_[(1S) was obtained. ) small cyclohexylethyl]-3-[(2'-mercapto-5,6-dihydrospiro[benzo[1,2 seven:5,4 七仁吱11南_3,3,_51 bow 丨哚]-Γ(2Ή)-yl) fluorenyl] acesulfame (87%), colorless solid: 1hnmr (3〇〇MHz, CDC13) δ 7.80 (d, J = 6.1, 1H), 7.64-7.57 (m, 1H), 7.46-7.36 (m, 2H), 7.23-7.15 (m, 2H), 7.07-7.00 (m, 1H), 6.79 (d, J = 7.7 Hz, 1H), 6.51 (s, 1H) ), 6.43 (s, 1H), 5.89 (d, J = 9.0 Hz, 1H), 5.08 (d, J = 15.7 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.92 (d, J = 15.7 Hz, 1H), 4.71 (d, J = 9.0 Hz, 1H), 4.55 (t, J = 8.6 Hz, 2H), 3.06-2.95 (m, 2H), 1.85-1.61 (m, 5H), 1.58 (s, 3H), 1.49-1.35 (m, 1H), 1.19-0.97 (m, 6H); MS (ES+) m/z 523.1 (M + 1). Example 12.7 N-[(1R)-1- ring Hexylethyl]-3-[(2'--yl-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-吲哚] Synthesis of -1'(_2Ή)-yl)mercapto]benzamide

Following the procedure as described in Example 12, and carrying out an insignificant change, replacing the cyclohexanemethylamine with (RH-)-l-cyclohexylethylamine gave N_[(1R)small cyclohexylethyl]-3 -[(2'-Crystal-5,6-di-spiro[benzo[l,2-b: 5,4-b'] two bite--3,3^5丨哚]-1' (2Ή )-yl)methyl]benzamide (60%) as a colorless solid: 1H NMR (300 MHz, CDCI3) δ 7.80 (d, J = 6.1, 1H), 7.64-7.57 (m, 1H), 7.46-7.36 (m, 2H), 7.23-7.15 (m, 2H), 7.07-7.00 (m, 1H), 6.79 (d, J = 7.7 Hz, 1H), 6.51 (s, 1H), 6.43 (s, 1H), 5.89 (d, J = 9.0 Hz, 1H), 5.08 (d, J = 15.7 Hz, 1H), 4.99 (d, J = 9.0 Hz, 1H), 4.92 (d, J = 15.7 Hz, 1H) , 4.71 (d, J = 9.0 Hz, 1H), 4.55 (t, J = 143924-sp.20091127-5 -790- 201020257 8.6 Hz, 2H), 3.06-2.95 (m, 2H), 1.85-1.61 (m , 5H), 1.58 (s, 3H), 1.49-1.35 (m, 1H), 1.19-0.97 (m, 6H); MS (ES+) m/z 523.1 (M + 1) e Example 12.8 N-(4- Ethylphenyl)-2-[(2·-mercapto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxan-3,3'-吲Synthesis of 哚]-Γ(2Ή)-yl)methyl]benzamide

.0, in accordance with the procedure as described in Example 12, and performing irrelevant changes, replacing cyclohexanemethylamine with 4-ethylaminobenzene, and using 2-[(2'-keto-5,6) -Dihydrospiro[benzo[Ub:5,4-7]difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-keto- 5,6-dihydrospiro[benzo[l,2-b:5,4-b1]difuran-3,3,-thirsty]-indole (2Ή)-yl)methyl]benzoic acid, N -(4-ethylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3W丨哚]-1'(2Ή)-yl)methyl]phenylguanamine (87%) as a colorless solid: mp. 23 (TC; 4 NMR (300 ΜΗζ, DMSO-d6) δ 10.50 (s, 1Η), 7.68-7.55 (m, 3H), 7.49-7.35 (m, 2H), 7.23-7.10 (m, 5H), 6.99 (dd, J = 7.5, 7.5 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 6.51 (s, 1H), 6.39 (s, 1H), 5.15-4.99 (m, 2H), 4.83 (d, J = 8.9 Hz, 1H), 4.68 (d, J = 8.9 Hz, 1H), 4.46 (t, J = 8.7 Hz, 2H), 2.99-2.85 (m, 2H), 2.54 (q, J = 7.5 Hz, 2H), 1.14 (t, J = 7.5Hz, 3H); 13CNMR( 75MHz, DMSO-d6) 5 177.8,167.4,161.6, 161.2, 142.8, 139.7, 137.2, 136.7, 134.4, 132.7, 130.8, 12 9.1, 129.3, 127.8, 127.1, 124.1, 123.6, 120.9, 120.4, 120.3, 119.6, 109.7, 92.9, 80.4, 72.6, 57.4, 143924-SD-20091127-5 791 - 201020257 41.5, 28.8, 28.1, 16.3 ; MS ( ES+) m/z 517.2 (Μ + 1). Example 12.9 Ν-(2-ethylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[i,2- b: Synthesis of 5,4-b,]difuran-3,3'-indole]-indole (2Ή)-yl)methyl]

Following the procedure as described in Example 12, and carrying out irrelevant changes, the use of 2-ethylaminobenzene to replace cyclohexanemethylamine, and the use of 2-[(2,-_yl-5,6-dihydrospiro) [Benzo[l,2-b: 5,4-7]difuranium]-1,(2Ή)-yl)indolyl]benzoic acid substituted 3-[(2'-keto-5,6-di Hydrogen snail [benzo[l,2-b:5,4-b,]difuran-3,3,-吲哚]-indole (2Ή)-yl)methyl]benzoic acid to obtain N-(2) -ethylphenyl)-2-[(2,-keto-5,6-dihydrospiro[benzo[1,2-b: 5,47']difuran-3,3W丨哚]- 1'(2Ή)-yl)methyl]benzamide (95%) as colorless solid: mp 184-186 ° C; 4 NMR (300 MHz, DMSO-d6) (5 10.06 (s, 1H), 7.69-7.61 (m,1H), 7.50-7.34 (m,3H),7.31-7.13 ❹ (m, 6H), 7.01 (dd, J = 7.5, 7.5 Hz, 1H), 6.90 (d, J = 7.8 Hz , 1H), 6.53 (s, 1H), 6.40 (s, 1H), 5.20-5.01 (m, 2H), 4.86 (d, J = 8.9 Hz, 1H), 4.72 (d, J = 8.9 Hz, 1H) , 4.47 (t, J = 8.7 Hz, 2H), 2.93 (t, J = 8.7 Hz, 2H), 2.68 (q, J = 7.5 Hz, 2H), 1.16 (t, J = 7.5 Hz, 3H) ; 13C NMR (75 MHz, DMSO-d6) 5 177.9, 168.1, 161.6, 161.2, 142.8, 139.8, 136.4, 135.8, 134.5, 132.7, 130 .8, 129.1, 129.0, 128.3, 127.9, 127.8, 127.0, 126.9, 126.5, 124.2, 123.6, 120.9, 120.4, 119.6, 109.7, 92.9, 80.4, 72.6, 57.5, 41.4, 28.8, 24.5, 14.8; MS (ES+ m/z 143924-sp-20091127-5 -792- (8) 201020257 517.2 (Μ+1) 〇Example 12.10 Ν-(2,4-dimethylphenyl)_2_[(2'-keto-5,6) Synthesis of dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3·-啕哚]-indole (2Ή)-yl)methyl]benzamine

Following the procedure as described in Example 12, and carrying out irrelevant changes, replacing cyclohexane decylamine with 2,4-diphenylaniline and using 2-[(Ζ-keto-5,6-dihydrospiro) [Benzo[1,2-b: 5,4-b']difuran 哚]-1·(2Ή)-yl)indolyl]benzoic acid substituted 3-[(Τ-keto-5,6 - Dihydrospiro[benzo[l,2-b ·· 5,4 7']difuran-3,3·-啕哚]-Γ(2Ή)-yl)indenyl]benzoic acid, obtained Ν-( 2,4-Dimethylphenyl)-2-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-7]difuran-3,3 ·-吲哚]-1'(2Ή)-yl)indolyl] benzoguanamine (90%) as a colorless solid: mp 207-208. (: ; 1H NMR (300 〇MHz, DMSO-d6) δ 9.95 (s, 1Η), 7.69-7.61 (m, 1H), 7.49-7.34 (m, 2H), 7.31-7.13 (m, 4H), 7.09 -6.95 (m, 3H), 6.89 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.40 (s, 1H), 5.20-5.01 (m, 2H), 4.86 (d, J = 8.9 Hz, 1H), 4.71 (d, J = 8.9 Hz, 1H), 4.47 (t, J = 8.7 Hz, 2H), 2.93 (t, J = 8.7 Hz, 2H), 2.25 (s, 6H); 13 C NMR (75 MHz, DMSO-c^) δ 177.9, 167.7, 161.6, 161.2, 142.8, 136.6, 135.6, 134.4, 133.9, 133.5, 132.7, 131.3, 130.8, 129.1, 128.4, 127.8, 126.9, 126.7, 124.2, 123.6 , 120.9, 120.4, 119.6, 109.7, 92.9, 80.4, 72.6, 65.4, 57.5, 41.4, 28.8, 21.0, 18·4, 15.6; MS (ES+) m/z 517.2 (M+l) 143924-sp-20091127 -5 -793- 201020257 Example 12.11 Furan N-(2-indolylphenyl)_2-[(2'-keto_5,6-dihydrospiro[benzo-like seven:5 4-7,] two

Following the procedure as described in Example 12, and carrying out irrelevant changes, o-methoxyaniline was used to replace cyclohexanemethylamine, and 2_[(2,-keto-5,6-dioxan] was used. Benzo[l,2-b: 5,47']difuran·3,3'_吲哚]-1,(2Ή)-yl)indolyl]benzoic acid replacement 3-[(2'-ketone) Benzyl-5,6-dihydrospiro[benzo-like seven:5,4-b1]difuran-3,3'-吲嗓Η'(2Ή)-yl)methyl]benzoic acid, obtaining N_(2 _曱Oxyphenyl)_2_[(2,_keto_5,6-dihydrospiro[benzo[l,2-b: 5,4-b.]difuran-3,3·-啕哚]- Γ(2Ή)-yl)methyl]benzoguanamine (84%) ' is a colorless solid: mp 172. 4 NMR (300 MHz, DMSO-d6) δ 9.66 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 7.0 Hz, 1H), 7.49-7.32 (m, 2H), 7.24-6.86 (m, 8H), 6.52 (s, 1H), 6.40 (s, 1H), 5.19-5.00 (m, 2H), 4.86 (d, J = 9.4 Hz, 1H), 4.70 (d , J = 9.4 Hz, 1H), 3.79 (s, 3H), 2.93 (t, J = 8.7 Hz, 2H); 13 C NMR (75 MHz, DMSO-d6) &lt;5 177.9, 167.6, 161.6, 161.2, 152.1, 142.8, 136.5, 134.4, 132.6, 130.8, 129.1, 128.2, 127.8, 127.1, 126.8, 126.5, 124.9, 124.1, 123.6, 120.9, 120.7, 120.4, 119.6, 112.0, 109.7, 92.9, 80.4, 72.6, 57.4, 56.2, 41.4, 28.8; MS (ES+) m/z 519.2 (M + 1). Example 12.12 N-(2-Fluorophenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran 143924- Sp-20091127-5 -794- (S) 201020257 -3,3·-吲嗓]-1'(2Ή)-yl)methyl]phenylamine synthesis

F. Following the procedure as described in Example 12, and carrying out irrelevant changes, 2-fluoroaniline was used to replace cyclohexane decylamine, and 2-[(2·-keto-5,6-dihydrospiro® was used). [Benzo[Ub: 5,4-b']difuran-3,3·-吲哚]-indole (2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-keto-5, 6-Dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3·-啕哚]-Γ(2Ή)-yl)methyl]benzoic acid, obtained Ν- (2-fluorophenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-啕哚]-Γ(2Ή&gt;yl)methyl]phenylguanamine (57%) as a colorless solid: mp 195-197 ° C; 4 NMR (300 MHz, DMSO-d6) δ 10.37 (s, 1 Η) , 7.75-7.59 (m, 2H), 7.51-7.35 (m, 2H), 7.34-7.11 (m, 6H), 7.00 (dd, J = 7.4, 7.4 Hz, 1H), 6.87 (d, J = 7.8 Hz , 1H), 6.52 (s, 1H), 6.40 (s, 1H), 5.19-5.00 (m, 2H), 4.85 (d, J = 9.4 Hz, 1H), 4.70 (d, J = 9.4 Hz, 1H) , ® 4.47 (t, J = 8.8 Hz, 2H), 2.93 (t, J = 8.8 Hz, 2H); 13C NMR (75 MHz, DMSO-d6) δ 177.8, 161.6, 161.2, 142.8, 135.8, 134.6, 132.7 , 131.1, 129.1, 128.6, 127.8, 127.4, 127.3, 127.0, 126.0, 125.8, 124.8, 124.7, 124.2, 123.6, 120.9, 120.4, 119.6, 116.4, 116.2, 109.7, 92.9, 80.5, 72.6, 57.5, 41.4, 28.8; MS (ES+) m/z 529.2 (M + 23). Example 12.13 N-(3 -Chlorophenyl)-2-[(T-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran 3,3'_叫丨嗓]- Synthesis of 1,(2Ή)-yl)methyl]benzamide 143924-sp-20091127-5 •795· 201020257 Ο

Following the procedure as described in Example 12, and carrying out irrelevant changes, 3-cycloaniline was used to replace cyclohexane decylamine, and 2-[(2'-keto-5,6-dihydrospiro[benzene] was used. And [1, 2 7: 5, 4 7 '] difuran-3,3'-吲哚]-1'(2'11)-yl)methyl]benzoic acid substituted 3-[(Ζ-keto- 5,6-dihydrospiro[benzo[l,2-b: 5,4-b.]difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzoic acid, Obtaining Ν-(3-phenylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3, 3'-吲哚]-Γ(2Ή)-yl) fluorenyl]benzamide (81%) as colorless solid: melting point &gt;230 °C; iHNMRGOOMHiDMSOO &lt;5 10.71 (s, 1H), 7.96- 7.90 (m, 1H), 7.65-7.57 (m, 2H), 7.52-7.31 (m, 3H), 7.26-7.10 (m, 4H), 6.99 (dd, J = 7.4, 7.4 Hz, 1H), 6.87 ( d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.38 (s, 1H), 5.16-4.99 (m, 2H), 4.82 (d, J = 9.4 Hz, 1H), 4.67 (d, J = 9.4 Hz, 1H), 4.46 (t, J = 8.8 Hz, 2H), 3.01-2.83 (m, 2H) ; 1 3 C NMR (75 MHz, DMSO-d6) (5 177.8, 167.8, 161.6, 161.2, 142.8, 140.9, 136.1, 134.5, 133.5, 132.7, 131.1, 130.8, 129.1, 128.5, 127.9, 127.4, 124.1, 12 3.9, 123.6, 120.9, 120.3, 119.8, 119.6, 118.7, 109.8, 92.9, 80.4, 72.6, 57.4, 41.7, 28.8; MS (ES+) m/z 523.1 (M + 1). Example 12.14 N-(3-Fluorine 2-mercaptophenyl)-2-[(2·-keto-5,6-dihydrospiro[benzo[ub:5,4-b']difuran-3,3·-啕哚Synthesis of Η·(2Ή)·yl) fluorenyl]benzamide 143924-SP-20091127-5 -796- 201020257

Following the procedure as described in Example 12, and carrying out irrelevant changes, the use of 3-fluoro-2-methylaniline in place of cyclohexanemethylamine and the use of 2_[(2,-keto-5,6- - Hydrogen snail [benzo[i,2_b : 5,4-b,]difuran-3,34丨哚]-1,(2Ή)-yl)methyl] ® benzoic acid replacement 3_[(2'- Keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]difuran-3,3,-bow h]-Γ(2Ή)-yl)methyl] Benzoic acid, obtained Ν_(3_fluoro-2-_2-methylphenyl)_2_ [(2'-keto-5,6-dihydrospiro[benzo[i,2_b : 5,4-b'] Furan-3,3,-嘀哚]-1,(2Ή)-yl)methyl]benzamide (84%) as colorless solid: melting point &gt;230°c; iHNMR (300 MHz, DMSO-d6 &lt;5 10.23 (s, 1H), 7.68 (d, J = 6.6 Hz, 1H), 7.51-7.37 (m, 2H), 7.33-7.13 (m, 5H), 7.11-6.97 (m, 2H), 6.89 (d, J = 7.8 Hz, 1H), 6.58 (s, 1H), 6.39 (s, 1H), 5.16-5.02 (m, 2H), 4.85 (d, J = 9.4 Hz, 1H), 4.70 (d , J = φ 9.4 Hz, 1H), 4.47 (t, J = 8.8 Hz, 2H), 2.93 (t, J = 8.8 Hz, 1H), 2.21-2.14 (m, 3H) ; 13C NMR (75 MHz, DMSO -d6) δ 177.8, 167.8, 162.8, 161.6, 161.2, 159.6, 142.8, 138.3, 138.2, 136.1, 134. 6, 132.7, 131.0, 129.1, 128.5, 127.9, 127.1, 127.0, 126.9, 124.2, 123.6, 122.7, 121.1, 126.9, 120.3, 119.6, 113.0, 112.7, 109.7, 92.9, 80.4, 72.6, 65.4, 57.4, 41.4, 28.8, 15.6, 10.4, 10.3 ; MS (ES+) m/z 543.1 (M +23). Example 12.15 Team Heptyl-2-[(2'-keto-5,6-dihydrospiro[stupid [1,2 7:5,4 7']difuran-3,3'-啕哚]- Synthesis of 1·(2Ή)-yl)fluorenyl]benzamide 143924-sp-20091127-5 -797- 201020257

Following the procedure as described in Example 12, and carrying out irrelevant changes, the cyclohexylamine was replaced with heptylamine and 2-[(2,-keto-5,6-dihydrospiro[benzo[ 1,2-b: 5,4-b·]difuran-3,3,-吲哚]-1,(2Ή)-yl)methyl]benzoic acid replacing 3-[(2'-keto- 5,6-dihydrospiro[benzo-like seven:5,4_b,]difuran_3,3,_吲哚]_r(2,H)-yl)methyl]benzoic acid, obtaining N-heptyl- 2-[(2,-keto-5,6-dihydrospiro[benzo-[l,2-b:5,4-b']difuran-3,3'-吲哚]-1, ( 2Ή)-yl)methyl]benzoguanamine (75%), as colorless solid: mp 1% - 198 ° C; iHNMR pOOMHz 'DMSO-de) δ 8.53 (t, J = 5.5 Hz, 1H), 7.46- 7.27 (m, 3H), 7.23-7.06 (m, 3H), 6.99 (dd, J = 7.5, 7.5 Hz, 1H), 6.84 (d, J = 7.7 Hz, 1H), 6.51 (s, 1H), 6.40 (s, 1H), 5.10=-4.92 (m, 2H), 4.85 (d, J = 9.4 Hz, 1H), 4.71 (d, J = 9.4 Hz, 1H), 4.55-4.39 (m, 2H), 3.23 (q, J = 6.8 Hz, 2H), 3.03-2.84 (m, 2H), 1.59-1.44 (m, 2H), 1.38-1.14 (m, 8H), 0.81 (t, J = 6.6 Hz, 1H); 13C NMR (75 MHz, DMSO-de) δ 177.8, o 168.7, 161.6, 161.2, 142.8, 136.9, 134.1, 132.6, 1 30.4, 129.1, 128.1, 127.8, 126.8, 124.1, 123.6, 120.9, 120.3, 119.6, 109.6, 92.9, 80.4, 72.6, 57.4, 41.3, 31.7, 29.4, 28.9, 28.8, 26·9, 22·5, 14.4; MS (ES+) m/z 511.2 (M + l). Example 12.16 N-(2-Galyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3 ,3,-吲哚]-1,(2Ή)-yl)mercapto]] Synthesis of benzamide 143924-SP-20091127-5 • 798-

201020257

Follow the procedure as described in Example 12, and perform an insignificant change' to replace cyclohexanemethylamine with 2-chlorodecylamine and use 2_[(2,-keto-5,6-di-spiro[ Benzo[l,2-b:5,47']difuran-3,3,,哚]-1,(2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-keto- 5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]difuran-3,3,-吲9 ^ 11 wood]-1'(2Ή)-yl)methyl] Benzoic acid, obtaining N_(2-chlorobenzyl)_2_[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b·]difuran-3 ,3·-啕哚]-1·(2Ή)-yl) fluorenyl] benzoic acid (88%) as a colorless solid: mp 148-150 Τ: ; 4 NMR (300 ΜΗζ, DMSO-d6) δ 9.12 (t, J = 5.8 Hz, 1H), 7.57 (dd, J = 7.2, 1.5 Hz, 1H), 7.51-7.24 (m, 6H), 7.23-7.11 (m, 3H), 7.00 (dd, J = 7.2 , 7.2 Hz, 1H), 6.86 (d, J = 7.7 Hz, 1H), 6.52 (s, 1H), 6.40 (s, 1H), 5.15-4.95 (m, 2H), 4.86 (d, J = 9.4 Hz , 1H), 4.71 (d, J = 9.4 Hz, 1H), 4.57-4.41 (m, 2H), 3.01-2.88 (m, 2H) ; 13 C NMR (75 MHz, DMSO-d6) &lt;5 177.8 , 169.0, 161.6, 161.2, 142.8, 136.6, 135.9, 134.6, 132.6, 132.5, 130.8, 129 .7, 129.4, 129.2, 129Λ, 128.4, 127.7, 127.0, 124.2, 123.6, 120.9, 120.4, 119.6, 109.7, 92.9, 80.4, 72.6, 57.4, 41.4, 41.1, 28.8; MS (ES+)m/z 537.2 ( M + l). Example 12.17 Γ-[2-(hexahydropyridin-1-ylcarbonyl)-yl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3, Synthesis of 3'-choline]-2'(1Ή)-ketone 143924-SP-20091127-5 -799- 201020257

P o Following the procedure as described in Example 12, and carrying out irrelevant changes, replacing the cyclohexanemethylamine with hexahydropyridine and using 2-[(2·-keto-5,6-dihydrospiro[ Benzo[l,2-b:5,4-b']difuran-3,3% 哚]-1'(2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-keto) -5,6-dihydrospiro[benzo[l,2-b: 5,4-b']dipyran-3,3'-吲嗓]-Γ(2Ή)-yl)methyl]benzene f Acid, Γ-[2-(hexahydropyridin-1-ylcarbonyl)aryl]&gt;5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3 , 3'-蚓哚]-2'(1Ή)-one (88%), as colorless solid: mp 168-170 ° C; iHNMR (300 MHz, DMSO-d6) 5 7.42-7.10 (m, 6H), 6.99 (dd, J = 7.5, 7.5 Hz, 1H), 6.65-6.44 (br, 1H), 6.39 (s, 1H), 4.90-4.64 (m, 4H), 4.54-4.39 (m, 2H), 3.77- 3.42 (br, 2H), 3.21-3.07 (m, 2H), 2.94 (t, J = 8.2, 1.5 Hz, 1H), 1.66-1.33 (m, 6H) ; 13C NMR (75 MHz, DMSO-d6) &lt;;5 177.7, 167.9, 161.6, 161.2, 142.7, 136.4, 132.6, 129.6, 129.1, 128.1, 126.6, 124.1, 123.5, 120.9, 120.3, 109.8, 92.9, 80.5, 72.6, 65.4, 57.4, 47.9, 42.3, φ 41.4 , 28.8, 26.4, 25.7, 24.4, 15.6; MS (ES+) m/z 481.2 (M + 1). Example 12.18 N-butyl-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran-3,3·-&lt; Synthesis of 哚]-1'(2Ή)-yl) benzyl]benzamide

-800- 143924-sp-20091127-5 (8) 201020257

Follow the procedure as described in Example 12, and perform irrelevant changes' using butylamine to replace cyclohexane decylamine and use 2-[(2'-keto-5,6-dihydrospiro[benzo[ 1,2-b: 5,4-b,]difuran-3,3'-indole]-indole (2Ή)-yl)methyl]benzoic acid substituted 3-[(2,-keto-5, 6-Dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3,3'-吲哚]-11(2'indolyl)methyl]benzoic acid, obtained Ν- Butyl-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-沔丨哚]- 1·(2Ή)-yl)methyl]benzamide (77%) ' is a colorless solid: mp 176-178 ° C; 4 NMR (300 MHz, CDC13) 5 7.48-7.41 (m, 1H), 7.37 -7.14 (m, 6H), 7.09-6.99 (m, 3H), 6.55-6.37 (m, 3H), ® 5.25-5.07 (m, 2H), 4.94 (d, J = 9.0 Hz, 1H), 4.70 ( d, J = 9.0 Hz, 1H), 4.52 (t, J = 8.2 Hz, 2H), 3.47 (q, J = 6.6 Hz, 2H), 2.98 (t, J = 8.7 Hz, 2H), 1.67-1.55 ( m, 2H), 1.50-1.35 (m, 2H), 0.95 (t, J = 6.6 Hz, 1H); MS (ES+) m/z 491.1 (M + 23). Example 12.19 N-(3-mercaptobenzene ))-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-啕哚]-Γ (2 ) - Synthesis of-yl) methyl] benzoyl amine of

Following the procedure as described in Example 12, and carrying out irrelevant changes, m-hexane aniline was used to replace cyclohexanemethylamine, and 2-[(2'-keto-5,6-dihydrospiro[benzene] was used. And [l,2-b: 5,47']difuran_3,3,_吲哚]-1'(2Ή)-yl)indenyl]benzoic acid substituted 3-[(2'-keto- 5,6-dihydrospiro[benzoxl,2-b:5,4-b,]difuran-3,3,-吲143924-sp-20091127-5 - 801 - 201020257 哚]-1' (2Ή )-yl)mercapto]benzoic acid to obtain N-(3-mercaptophenyl)-2-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5] , 4-b·]difuran-3,3^ 哚 哚]-Γ(2Ή)-yl) fluorenyl]benzamide (81%) as a colorless solid: mp 229-231. (: ; 4 NMR (300 MHz, CDC13) δ 8.85 (s, 1H), 7.64-7.55 (m, 2H), 7.49-7.42 (m, 1H), 7.40-7.33 (m, 2H), 7.32-7.16 ( m, 4H), 7.11-7.03 (m, 2H), 6.96 (d, J = 7.6 Hz, 1H), 6.40 (s, 2H), 5.22-5.05 (m, 2H), 4.93 (d, J = 9.0 Hz , 1H), 4.67 (d, J = 9.0 Hz, 1H), 4.52 (t, J = 8.7 Hz, 2H), 2.96 (t, J = 8.5 Hz, 2H), 2.35 (s, 3H) ; MS (ES+ m/z 525.11 (M +23). Example 12.20 ❹ 1^-(2-Fluoro-5-methylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzene] And [1,2-1): 5,4,7,] Synthesis of difuran-3,3'-吲哚]-1'(2·Η)-yl)methyl]benzamide

Following the procedure as described in Example 12, and carrying out irrelevant changes, 2-fluoro-5-methylaniline was substituted for cyclohexaneguanamine and 2_[(2,-keto-5,6- was used). Dihydrospiro[benzo[l,2-b:5,4-b,]difuran·3,3,_decade]-Γ(2Ή)-yl)indolyl] benzoic acid replacement 3-[(2 '-Mercapto-5,6-dihydrospiro[benzo(^7:5,47']difuran-3,3'-啕哚]-Γ(2Ή)-yl)indolyl]benzoic acid' Obtained Ν (2-fluoro-5-methylphenyl)_2_ [(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-b']difuran- 3,3^5丨哚]-1,(2Ή)-yl)indolyl]benzamine (77%) as a colorless solid: m.p. </ </ </RTI> </ </RTI> </ RTI> </ RTI> </ RTI> </ RTI> NMR (300 MHz, CDC13) δ 8.25- 8.06 (m, 2H), 7.65-7.57 (m, 1H), 7.47-7.33 (m, •802- 143924-sp-20091127-5 (s) 201020257 2H), 7.33-7.26 (m, 1H), 7.22- 7.12 (m, 2H), 7.07-6.86 (m, 4H), 6.46 (s, 1H), 6.40 (s, 1H), 5.27 (s, 2H), 4.95 (d, J = 9.0 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.52 (t, J = 8.7 Hz, 2H), 2.96 (t, J = 8.5 Hz, 2H), 2.36 (s, 3H) ; MS (ES+) m/z 543.1 (M + 23). Example 12.21 N-(2,3-Dimercaptophenyl)-2-[(2·-keto-5,6-di Spiro [benzo [l, 2-b: 5,4-b ·] difuran-3,3 - indol] -1 '(2Ή) - yl) methyl] benzoyl amine of

Following the procedure as described in Example 12, and performing irrelevant changes, replacing cyclohexanemethylamine with 2,3-dimethylaniline and using 2-[(2,-keto-5,6-dihydrol) Snail [benzo[l,2-b: 5,4-b']difuran-3,3W丨哚]-Γ(2Ή)-yl)methyl]benzoic acid substituted 3-[(2·-keto) -5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-吲

哚]-1'(2Ή)-yl)methyl]benzoic acid, obtained 2,3-didecylphenyl)·2_[(2,-keto-5,6-dihydrospiro[benzo[ l,2-b: 5,4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzamide (87%), colorless solid: melting point &gt ; 23〇. (: ; WNMR (300 MHz, CDC13) δ 7.98 (s, 1Η), 7.69-7.53 (m, 2H), 7.46-7.33 (m, 2H), 7.33-7.11 (m, 6H), 7.11-6.99 (m , 3H), 6.45 (s, 1H), 6.40 (s, 1H), 5.34-5.17 (m, 2H), 4.93 (d, J = 9.0 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H) , 4.52 (t, J = 8.7 Hz, 2H), 2.96 (t, J = 8.5 Hz, 2H), 2.32 (s, 3H), 2.22 (s, 3H) ; MS (ES+) m/z 539.1 (M + 23). Example 12.22 143924-sp-20091127-5 •803- 201020257 N-[2-(4-methoxyphenyl)ethyl; i_2-[(2'-keto-5,6-dihydrospiro[ Synthesis of Benzo[l,2-b:5,4-b·]difuran-3,3·-啕哚]-Γ(2Ή)-yl)indenyl]benzamide

Following the procedure as described in Example 12, and carrying out irrelevant changes, the use of 2-(4-methoxyphenyl)ethylamine in place of cyclohexane decylamine, and the use of 2_[(2'-keto-5, 6-Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲哚]-1,(2Ή)-yl)indolyl] benzoic acid substitution 3 -[(2'-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b1]difuran-3,3,-para-]-anthracene (2Ή)-yl Benzyl]benzoic acid, obtaining N_[2_(4_曱-oxyphenyl)ethyl]_2_ [(2'--yl-5,6-dihydrospiro[benzo[i,2-b: 5, 4-b,]difuran-3,3,-indole, (2Ή)-yl)methyl]benzamide (85%) as colorless solid: iH NMR (300 ΜΗζ, CDC13) δ 7.39- 7.13 (m, 8H), 7.08-6.95 (m, 2H), 6.86-6.78 (m, 2H), 6.52- 6.39 (m, 3H), 5.10-4.90 (m, 3H), 4.70 (d, J =: 9.0 Hz, 1H), 3.81-3.62 (m, 5H), 2.98 (t, J = 8.7 Hz, 2H), 2.90 (t, J = 8.7 Hz, 2H) ; MS (ES+) m/z 569.2 (M + twenty three). Example 12.23 N-(3-Azylbenzyl)-2-[(2'-keto-5,6-dihydrospiro[benzox,2_b:5,4-b,]difuran-3,3' -+Duoduo'(2Ή)-yl)methyl]benzoguanamine synthesis 143924-sp-20091127-5 -804- 201020257

P

Following the procedure as described in Example 12, and carrying out irrelevant changes, 3-cyclobenzylamine was used to replace cyclohexanemethylamine, and 2_[(2L keto-5,6-dihydrospiro[benzoyl] was used. [l,2-b: 5,47']difuran_3,3',哚]_ι'(2,Η)-yl)methyl]benzoic acid substituted 3-[(2'-keto-5 , 6-di-spiro[benzone, 2_b: 5,4-b·]difuran-3,3,-吲® P-based)methyl]benzoic acid, obtaining N-(3-chloro-aryl) )-2-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran_3,3|_ 哚; j-iCH )-yl)methyl]benzamide (84%) ' is a colorless solid: 1H NMR (3 〇〇MHz, CDCl3) 5 7 52_7 47 (m, 1H), 7.39-7.15 (m, 9H), 7.09 -7.00 (m, 3H), 6.44 (s, 1H), 6.40 (s, 1H), 5.21-5.06 (m, 2H), 4.93 (d, J = 9.0 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.62 (d, J = 5.9 Hz, 2H), 4.52 (t, J = 8.6 Hz, 2H), 2.95 (t, J = 8.6 Hz, 2H) ; MS (ES+) m/z 559.1 ( M + 23). Example 12.24 N-[2-(4-Phenylphenyl)ethyl]-2-[(2,-keto-5,6-dihydrospiro[benzox, 2,7:5,4-b,] Synthesis of dipyran-3,3'4丨哚H'(2'H)-yl)methyl]benzamide

Follow the procedure as described in Example 12, and perform irrelevant changes 143924-sp-20091127-5 • 805-201020257 Replace 2-cyclohexaneamine with 2-(4-phenylphenyl)ethylamine and use 2 -[(2,-fluorenyl-5,6-dihydrospiro[{,2-b: 5,4-b,]difuran-3,3,-峋哚Η, (2Ή&gt;) Benzyl]benzoic acid substituted 3-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-吲嗓]-Γ(2Ή)-yl)methyl]benzoic acid, obtaining N_[2_(4-phenylphenyl)ethyl]-2-[(2,-keto-5,6-dihydrospiro[benzene And [i,2_b: 5,4-b,]difuran-3,3,-啕哚]-indole (2Ή)-yl)indolyl]benzamide (78%) as a colorless solid: iHNMR ( 300MHz, CDCl3) 5 8.59 (br, 1H), 7.44-7.23 (m, 7H), 7.23-6.11 (m, 2H), 7.10-6.94 (m, 2H), 6.73 (d, J = 7.7 Hz, 1H) , 6.52 (s, 1H), 6.40 (s, 1H), 4.94-4.65 (m, 4H), 4.47 (t, J = 8.6 Hz, 2H), 3.57-3.42 (m, 2H), 2.95 (t, J = 8.3 Hz, 2H), 2.84 (t, J = 6.7 Hz, ® 2H); MS (ES+) m/z 573.1 (M + 23). Example 12.25 N-(2-Methoxyphenyl)-4-[ (2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]di-amino-3,3'-W哚]-l'(2 H) - yl) methyl] benzoyl amine of

Following the procedure as described in Example 12, and carrying out irrelevant changes, the cyclohexylamine was replaced with 2-decyloxyaniline and 4[(2, keto-5,6-dihydrospiro[benzene] was used. And [l,2-b: 5,4-b']difuran-3,3,-indenyl)indolyl]benzoic acid replaces 3-[(2-keto-5,6-dihydrospiro) [Benzo[^7:5,4-b']di-ββ__3,3,-ρ丨哚丨哚]-Γ(2Ή)-yl)indolyl]benzoic acid, obtained Ν_(2_曱Oxyphenyl)4_[(2,,yl_5,6·dihydrospiro[benzo[1'2-b: 5,47']difuran_3,3,_吲哚]_Γ(2Ή) _yl)methyl]benzamide (68%) ' is a colorless solid: 1H NMR p〇〇MHz, CDa3) 5 8 56 8 143924-SD-20091127-5 201020257 (m, 2H), 7.87 (d, J = 7.9 Hz, 2H), 7.45 (d, J = 7.9 Hz, 2H), 7.23-7.15 (m, 2H), 7.11-6.96 (m, 3H), 6.90 (d, J = 7.9 Hz, 1H), 6.76 (d, J = 7.9 Hz, 1H), 6.48 (s, 1H), 6.42 (s, 1H), 5.01 (ABq, 2H), 4.85 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H ), 3.90 (s, 3H), 3.07-2.92 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 178.0, 164.7, 161.9, 161.4, 148.1, 141.8, 139.7, 134.9, 132.7, 128.8, 127.8, 127.7, 127.6, 124.1, 124.0, 123.7, 12 1.2, 120.1, 120.0, 119.8, 118.9, 109.9, 109.1, 93.4, 93.3, 80.7, 72.4, 57.8, 55.8, 43.9, 29.1; MS (ES+) m/z 519.1 (M + 1). Example 12.26 ❹ 4-[(2'-_yl-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]difuran-3,3,-吲哚]-1 Synthesis of (2Ή)-yl)-yl]-[2-(trifluoromethyl)phenyl]benzamide

Following the procedure as described in Example 12, and carrying out irrelevant changes, the use of 2-(trifluoromethyl)aniline in place of cyclohexanemethylamine and the use of 4-[(2,-keto® _5,6- Dihydrospiro[benzo[l,2-b··5,4?']difuran-3,3,-(9)哚]-Γ(2Ή)-yl)methyl]benzoic acid substituted 3-[(2 '-keto-5,6-di-argon[benzo[1,2:7,5,7,7]difuran-3,3·-啕哚]-1'(211)-yl)methyl] Benzoic acid, 4-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-吲哚]- 1'(2Ή)-yl)methyl]-indole-[2-(trifluoromethyl)phenyl]benzamide (53%) as colorless solid: iHNMR (300MHz, CDCl3) δ 8.39 (d, J = 8.2 Hz, 1H), 8.17 (s, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.62 (dd, J = 15.9, 7.9 Hz, 2H), 7.48 (d, J = 8.2 Hz, 2H), 7.31-7.14 (m, 4H), 7.04 (dd, J = 7.6, 7.6, 0.7 Hz, 1H), 6.76 (d, J = 7.7 Hz, 1H), 6.47 (s, 1H), 6.43 (s , 1H), 5.02 143924-sp-20091127-5 -807- 201020257 (ABq, 2H), 4.85 (ABq, 2H), 4.54 (t, J = 8.7 Hz, 2H), 3.10-2.90 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 178.0, 164.9, 161.9, 161.3, 142.6, 141.7, 14 0.4, 133.8, 133.1, 132.7, 128.8, 128.0, 127.7, 126.2, 124.6, 124.1 (2C), 123.7, 120.0, 118.8, 109.0, 93.3, 80.6, 72.4, 57.7, 43.8, 29.0 ; MS (ES+) m/z 557.1 (M+l). Example 12.27 4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']di-n-but-3,3'-啕哚]-Γ Synthesis of (2Ή)-yl)methyl]-N-phenylbenzamide

Following the procedure as described in Example 12, and carrying out irrelevant changes, aniline was substituted for cyclohexanemethylamine and 4-[(Z-keto-5,6-dihydrospiro[benzo[1, 2-b: 5,4-b1]difuran-3,3,-吲哚]-indole (2Ή)-yl)methyl]benzoic acid replaces 3-[(2'-keto-5,6- Dihydrospiro[benzo[1,2:7:5,4-1)|]difuran-3,3'-'*??丨哚]-1|(2'11)-yl)methyl]phenylhydrazine Acid, 4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-b:5,4-b]difuran-3,3'-啕哚]-1' (2Ή)-yl) fluorenyl]-N-phenylbenzamide (90%) as colorless solid: 1H NMR (300 MHz, CDC13) 5 8.34 (s, 1 Η), 7.83 (d, J = 7.8 Ηζ, 2H), 7.60 (d, J = 8.3 Hz, 2H), 7.39-7.23 (m, 4H), 7.23-6.97 (m, 4H), 6.72 (d, J =7.7 Hz, 1H), 6.44 (s , 1H), 6.38 (s, 1H), 4.92 (ABq, 2H), 4.77 (ABq, 2H), 4.48 (t, J = 8.5 Hz, 2H), 2.89 (t, J = 8.5 Hz, 2H); 13 C NMR (75 MHz, CDC13) δ 178.1, 165.2, 161.8, 161.3, 141.6, 139.4, 137.9, 134.6, 132.4, 128.8, 128.7, 127.8, 127.4, 124.4, 123.9, 123.7, 120.2, 119.9, 119.7, 118.7, 109.1 , 93.2, 80.4, 72.3, 57.7, 43.7, 28.8 ; MS (ES+) m/z 489. 1 (M + 1). 143924-sp-20091127-5 -808- 201020257 Example 12.28 N-Methyl-4-[(2'--yl-5,6-dihydrospiro[benzo[u_b: 5,4-7,]di-p Synthesis of _3 to 嗓]-Γ(2Ή)·yl)methyl]benzamide

According to the procedure as described in Example 12, and irrelevant changes were made, the cyclohexanemethylamine was replaced with methylamine hydrochloride, and 4_[(2,-keto-5,6-dihydrostilbene] was used. Stupid [丨'2 7:5,4 7'] difuran-3,3,-&lt;哚]-1,(2Ή)-yl)indenyl]benzoic acid substituted 3-[(2'-yl) -5,6-dihydrospiro[benzo[12_b:5,4_b,]difuranium]-indole (2Ή)-yl)indenyl]benzoic acid to obtain N-methyl_4_[(2,-ketone) Base_56_dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-anthracene, (2Ή)-yl)methyl]benzamide ( 86%), as a colorless solid: iHNMR (300MHz, CDCl3) 5 7_71 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.22-7.12 (m, 2H), 7.02 ( t, J = 7.6 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 6.57-6.45 (m, 1H), 6.42 (s, 1H), 6.39 (s, 1H), 4.95 (ABq, 2H ), 4.81 (ABq, 2H), 4.53-4.34 (m, 2H), 2.95 (d, J = 4.0 Hz, 3H), 2.90-2.73 © (m, 2H) ; 13C NMR (75 MHz, CDC13) &lt; 5 178.2, 167.5, 161.9, 161.4, 141.8, 139.0, 134.2, 132.5, 128.8, 127.6, 127.4, 124.0, 123.7, 120.0, 119.8, 118.7, 109.2, 93.3, 80.6, 72.4, 57.7, 43.8, 28.9, 26.8; S (ES+) m/z 427.1 (M + 1). Example 12.29 N-(2-Fluorophenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran-3, Synthesis of 3·-吲哚]-1·(2Ή)-yl)fluorenyl]benzamide 143924-sp-20091127-5 -809- 201020257

Following the procedure as described in Example 12, and carrying out irrelevant changes, the cyclohexylamine was replaced with 2-fluoromethane, and 4_[(2,-keto-5,6-dihydrospiro[benzene] was used. And [1,2 7:5,4 7']difuran-3,3'-吲哚]-1,(2,11)-yl)indolyl]benzoic acid replaces 3-[(2'-ketone) -5,6-dihydrospiro[benzo[ι,2:7,5,4-b,]difuran-3,3,-indole]-indole (2Ή)-yl)methyl]benzoic acid, Obtaining Ν-(2-fluorophenyl)-4-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3, 3,-吲哚]-1,(2Ή)-yl)methyl]benzamide (75%) as a colorless solid: iHNMRGOOMHz 'CDCl»5 8.42 (ddd, J = 8.1, 8.1, 1.2 Hz, 1H), 8.16-7.99 (m, 1H), 7.88 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.1

Hz, 2H), 7.25-7.01 (m, 6H), 6.77 (d, J = 7.7 Hz, 1H), 6.49 (s, 1H), 6.43 (s, 1H), 5.03 (ABq, 2H), 4.86 (ABq , 2H), 4.55 (t, J = 8.6 Hz, 2H), 3.10-2.91 (m, 2H) ; 13 C NMR (75 MHz, CDC13) ¢5 177.9,164.8,161.8,161.3,152.7 (d, J = 243.1 Hz), 141.7, 140.1, 134.0, 132.6, 128.7, 127.7 (2C), 126.3 (d, J = 9.8 Hz, 2C), 124.7, 124.6 (d, J = 3.9 Hz), 124.0, 123.6, 121.8, 119.9 (2C), 118.7, 114.8 (d, J = 19.2 Hz, 2C), 109.0, 93.2, 80.6, 72.3, 57.7, 43.7, 29.0; MS (ES+) m/z 507.1 (M + 1). Example 12.30 4-[(2*-keto-5,6-dihydrospiro[benzo[1,2-1):5,4-7]]difuran-3,3'-4哚]-1' Synthesis of (2'11)-yl)mercapto]-N-(2-sulfen-2-ylethyl)benzoguanamine 143924-SO-20091127-5 -810· 201020257

Following the procedure as described in Example 12, and performing irrelevant changes, replacing cyclohexanemethylamine with 2-p-cepheneethylamine and using 4_[(2,-keto-5,6-dihydrospiro[ Benzo[1'2-b: 5,47']difuran_3,3,-encyclo]-Γ(2Ή&gt;-yl)fluorenyl]benzoic acid substituted 3-[(2'-keto) -5,6-dihydrospiro[benzo-like seven:5,4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl)methyl]benzoic acid' obtained 4_[( 2,_keto- 5,6-dihydrospiro[benzo[l,2-b:5,47']difuran-3,3·-吲哚]-1,(2Ή)-yl)曱]]-Ν-(2-ρ-cephen-2-ylethyl)benzamide (74%) as a colorless solid: iHNMR (300MHz, CDCl3), 7.71 (d, J = 7.9 Hz, 2H), 7.37 (d, J = 7.9 Hz, 2H), 7.24-7.13 (m, 3H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.95 (dd, J = 5.0, 3.5 Hz, 1H), 6.86 (d, J = 3.5 Hz, 1H), 6.74 (d, J = 7.6 Hz, 1H), 6.51-6.46 (m, 1H), 6.46 (s, 1H), 6.42 (s, 1H), 4.97 (ABq, 2H), 4.83 (ABq, 2H), 4.52 (t, J = 8.6 Hz, 2H), 3.78-3.57 (m, 2H), 3.13 (t, J = 6.2 Hz, 2H), 2.95 (t, J = 8.6 Hz, 2H) ; 13 C NMR (75 MHz, CDC13) φ &lt;5 177.9,166.8,161.8,161.3,141.7,141.1,139 .2,134.1,132.5, 128.7, 127.5, 127.4, 127.0, 125.4, 123.9 (2C), 123.6, 119.9 (2C), 118.7, 109.0, 93.2, 80.5, 72.3, 57.6, 43.7, 41.2, 29.8, 28.9; MS (ES+ m/z 523.1 (M + 1). Example 12.31 4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran- Synthesis of 3,3'-吲哚]-1·(2Ή)-yl)indolyl]benzamine

143924-sp-20091127-5 • 811- 201020257 Following the procedure as described in Example 12, and carrying out irrelevant changes, replace the cyclohexane methylamine with ammonia in anhydrous dichloromethane and use 4_[(2, -keto--5,6-dihydrospiro[benzo[i,2-b:5,4-b,]dipyran-3,3^5bdu]-1,(2Ή)-yl)A 3-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3'3W丨嗓]-1 '(2Ή)-yl)methyl]benzoic acid, 4_, keto- 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3' -吲哚]-ΐ·(2Ή)-yl) fluorenyl]benzamide (81%) as a colorless solid: 1 η NMR (300 MHz, CDC13) &lt;5 7.78 (d, J = 7.9 Ηζ, 2H), 7.34 (d, J = 7.9 Hz, 2H), 7.20-7.07 (m, 2H), 6.99 (t, J = 7.4 Hz, 1H), 6.85 (s, 1H), 6.71 (d, J = 7.6 Hz, 1H), 6.41 (br s, 1H), 6.35 (br s, 1H), 6.20 (s, 1H), 4.94 (ABq, 2H), 4.78 (ABq, 2H), 4.46 (t, J = 8.5 Hz , 2H), 2.91 (t, J = 8.5 Hz, 2H); 13C NMR (75 MHz, CDC13) (5 177.6, 168.7, 161.5, 160.9, 141.4, 139.3, 132.7, 132.1, 128.4, 127.8, 127.0, 123.6, 123.3, 119.6, 118.4, 108.8, 92.8, 80.2, 72.0, 57.3, 43.4, 28.6; MS (ES+) m/z 413.1 (M + 1). Example 12.32 N-(2,3-Dihydro-1H-indol-5-yl)·4 -[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,] di-pyran-3,3'-吲哚]-ΐ, (2Ή Synthesis of )-yl)methyl]benzamine

Following the procedure as described in Example 12, and carrying out insignificant changes, replacing cyclohexanemethylamine with 5-aminohydroquinone and using 4-[(2,-keto-5,6-dihydrospiro) [Benzo[l,2-b: 5,4-b']difuran-3,3,-(4)哚]-Γ(2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-ketone) -5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-啕哚]-1·(2Ή)-yl)indenyl]benzene Formic acid, obtained (2,3-dihydro-1H-indol-5-yl)-4-[(2,- 143924-sp-20091127-5 -812- 201020257 keto-5,6-dihydrospiro[ Benzo[i,2-b:5,4,7,difuran-3,3,-indole]-indole (2Ή)-yl)methyl]benzamide (65%) as a colorless solid: iHNMR (300MHz, CDCl3) δ 7.83 (d, J = 8.1 Hz, 2H), 7.79 (s, 1H), 7.56 (s, 1H), 7.42 (d, J = 8.1 Hz, 2H), 7.28-7.21 (m , 2H), 7.21-7.14 (m, 2H), 7.08-6.97 (m, 1H), 6.74 (d, J = 7.7 Hz, 1H), 6.46 (s, 1H), 6.42 (s, 1H), 4.99 ( ABq, 2H), 4.83 (ABq, 2H), 4.53 (t, J = 8.6 Hz, 2H), 3.03-2.80 (m, 6H), 2.15-1.97 (m, 2H) ; MS (ES+) m/z 529.1 (M + 1) 〇 Example 12.33 ® r_[4-(Nfofolin carbonyl) aryl]-5,6-dihydrospiro[benzo[l, 2-b : Synthesis of 5,4-b']difuran-3,3'-啕哚]-2'(1Ή)-嗣

Q Following the procedure as described in Example 12, and performing insignificant changes, replacing the cyclohexane methylamine with morpholine and using 4-[(2'-keto-5,6-dihydrospiro[ [ Benzo[Ub:5,4?']difuran-3,3·-峋哚]-1·(2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-keto-5,6 -Dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3'-indole-1'(2Ή)-yl)methyl]benzoic acid, obtained Γ- [4-(morpholine-4-ylcarbonyl)-yl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3·-啕哚]-2,(1Ή)-one (58%), as a colorless solid: 4 NMR (300 MHz, CDC13)5 7.44-7.35 (m, 4H), 7.24-7.15 (m, 2H), 7.04 (dd, J = 7.5, 7.5 Hz, 1H), 6.76 (d, J = 7.5 Hz, 1H), 6.48 (s, 1H), 6.44 (s, 1H), 4.98 (ABq, 2H), 4.85 (ABq, 2H), 4.55 (t, J = 8.6 Hz, 2H), 3.87-3.40 (m, 8H), 3.08-2.93 (m, 2H); MS (ES+) m/z 483.1 (M + 1). 143924-sp-20091127-5 -813- 201020257 Example 12.34 N-(2-ethylphenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b] ··5,4-b1 Difuran-3,3·-沔丨嗓]-Γ(2Ή)-yl)indenyl] Synthesis of Benzoyl Amine

Following the procedure as described in Example 12, and carrying out irrelevant changes, the use of 2-ethylaminobenzene to replace cyclohexanemethylamine and the use of 4-[(2'-keto-5,6-dihydrospiro) [Benzo[l,2-b:5,47']difuranium]-indole (2Ή)-yl)indolyl]benzoic acid substituted 3-[(2'-keto-5,6-di Hydrogen snail [benzo[1,2-7:5,47']difuran-3,3'-啕哚]-1'(2Ή)-yl)methyl]benzoic acid, obtained Ν-(2- Ethylphenyl)-4-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b]difuran-3,3·-吲哚] - Γ(2Ή)-yl) fluorenyl]benzamine (49%) as colorless solid: mp 203-204 ° C; W NMR (300 ΜΗζ, CDC13) δ 7.96-7.83 (m, 3H), 7.69 (s, 1H), 7.52-7.44 (m, 2H), 7.31-7.13 (m, 5H), 7.10-7.02 (m, 1H), 6.82-6.74 (m, 1H), 6.49 (s, 1H), 6.44 (s, 1H), 5.03 (ABq, 2H), 4.86 (ABq, 2H), 4.60-4.51 (m, 2H), 3.11-2.92 (m, 2H), 2.67 (q, J = 7.5 Hz, 2H), 1.27 (t, J = 7.5 Hz, 3H); 13 C NMR (75 MHz, CDC13) &lt;5 178.0, 165.2, 161.9, 161.3, 141.8, 139.8, 135.1, 134.9, 134.6, 132.7, 128.8, 128.6, 127.8, 127.7, 126.8, 125.8, 124.1, 123.7, 120.0, 119.9, 118.8, 10 9.1, 93.3, 80.6, 72.4, 57.7, 43.8, 29.0, 24.4, 14.0; MS (ES+) m/z 517.2 (M + 1). Example 12.35 N-(2,6-Dimercaptophenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b'] Synthesis of difuran-3,3'-indole]-indole (2Ή)-yl)indenyl]benzamide 143924-sp-20091127-5 -814· 201020257

Following the procedure as described in Example 12, and carrying out irrelevant changes, replacing cyclohexanemethylamine with 2,6-xylyleneamine and using 4-[(2 fluorenyl-5,6-dihydrospiro) [Benzo[l,2-b: 5,47']difuran-3,3W丨哚]-1'(2Ή)-yl)methyl]benzoic acid replaces 3-[(2'-keto) -5,6-dihydrospiro[benzo[1,2-b : 5,4-b,]difuran-3,3,-啕哚Η·(2Ή)-yl)indolyl]benzoic acid, Obtaining N-(2,6-dimethylphenyl)-4-[(2,-_yl-5,6-dihydrospiro[benzo[l,2-b:5,4?']difuran -3,3'-啕哚]-1'(2Ή)-yl)methyl]benzamide (28%) as a colorless solid: mp. (: ; iHNMRQOOMHz, CDC13) &lt;5 7.95-7.89 (m, 2H), 7.51-7.45 (m, 2H), 7.37 (s, 1H), 7.24-7.02 (m, 6H), 6.82-6.75 (m, 1H), 6.49 (s, 1H), 6.44 (s, 1H), 5.04 (ABq, 2H), 4.86 (ABq, 2H), 4.60-4.50 (m, 2H), 3.12-2.91 (m, 2H), 2.27 (s, 6H) ; 13C NMR (75 MHz, CDCI3) δ 178.0, 165.3, 161.9, 161.4, 141.8, 139.8, 135.5, 134.1, 133.6, 132.7, 128.8, 128.3, 127.9, 127.8, 127.6, 124.0, 123.7, 120.0 , 118.8, 参(10).1' 93·3, 80.7, 72.4, 57.8, 43.8, 29.0, 18.5; MS (ES+) m/z 517.2 (Μ + 1). Example 12.36 N-(3-Fluorophenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-1)1]difuran- Synthesis of 3,3 W丨嗓]-1'(2Ή)-yl)indolyl]benzamide

Following the procedure as described in Example 12, and performing an insignificant change 143924-sp-20091127-5 -815-201020257, replacing cyclohexanemethylamine with 3-fluoroaniline, and using 4-[(2'-keto) -5,6-dihydrospiro[benzo[1,2-b: 5,4-b']difuran-3,3'-throindole-1'(2Ή)-yl)methyl]phenylhydrazine Acid replacement of 3-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3Ή丨哚]-Γ(2Ή) -yl) fluorenyl]benzoic acid, obtained Ν-(3-fluorophenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7 ']Difuran-3,3|-啕哚]-11(2'11)-yl)methyl]phenylhydrazine (50%) as colorless solid: melting point &gt;250 °C; iHNMROOOMHtCDCls) 5 8.03 (s, 1H), 7.89-7.82 (m, 2H), 7.63-7.56 (m, 1H), 7.48-7.41 (m, 2H), 7.34-7.15 (m, 4H), 7.09-7.01 (m, 1H) , 6.89-6.80 (m, 1H), 6.78-6.72 (m, 1H), 6.47 (s, 1H), 6.42 (s, 1H), 5.01 (ABq, 2H), 4.82 (ABq, 2H), 4.57-4.48 (m, 2H), 3.01-2.92 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 178.3, 163.6 (d, Jc. F = 248.0 Hz), 161.4, 141.7, 139.7, 139.5 (d, JC .F= 10.8 Hz), 134.3, 132.4, 130.0 (d, JC.F = 9.4 Hz), 128 .8, 127.9, 127.6, 124.1, 123.8, 120.0, 119.7, 118.7, 115.4 (d, Jc-F= 2.9 Hz), 111.2 (d, JC.F= 21.3 Hz), 109.2, 107.6 (d, JC.F = 26.4 Hz), 93.3, 80.5, 72.4, 57.8, 43.8, 28.9; MS (ES+) m/z 507.2 (M + 1). Example 12.37 N-(2,4-Dimethylphenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-b: 5,4-b,] Synthesis of difuran-3,3'-state 哚]-1'(2Ή)-yl)methyl]benzoguanamine

Replacement of cyclohexanemethylamine with 2,4-dinonylaniline and use of 4-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-7'] Difuran_3,3,_吲哚]-Γ(2Ή)-yl)indenyl]benzoic acid substituted 3-[(2'-keto-5,6-dihydrospiro[stuppytl, 2-b : 5,4-b,]difuran-3,3,-W 143924-sp-20091127-5 816- 201020257 哚]-Γ(2Ή)-yl)methyl]benzoic acid, obtaining N-(2,4 -Dimethylphenyl)-4-[(2,-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3'-吲哚]-Γ(2Ή)-yl)methyl] benzoguanamine (59%) as a colorless solid: mp 249-251. (: ; 1H NMR (300 MHz, CDC13) δ 7.91-7.83 (m, 2Η), 7.76-7.69 (m, 1H), 7.56 (s, 1H), 7.50- 7.43 (m, 2H), 7.28-7.17 ( m, 2H), 7.09-7.01 (m, 3H), 6.80-6.74 (m, 1H), 6.49 (s, 1H), 6.44 (s, 1H), 5.03 (ABq, 2H), 4.86 (ABq, 2H) , 4.60-4.51 (m, 2H), 3.11-2.92 (m, 2H), 2.32 (s, 3H), 2.28 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 178.0, 165.2, 161.9, 161.3 , 141.7, 139.6, 135.3, 134.6, 132.9, 132.6, 131.2, ® 129.8, 128.7, 127.7, 127.4, 124.0, 123.6 (2C), 120.0 (2C), 118.8, 109.1, 93.3, 80.6, 72.4, 57.7, 43, 8, 29.0, 20.9, 17.8; MS (ES+) m/z 517.2 (M + 1). Example 12.38 4-[(2'-keto-5,6-dihydrospiro[benzo[1,2:7: Synthesis of 5,4-b,]difuran-3,3,-anthracene-fluorenyl (2Ή)-yl)indolyl]-indole-dexoster-2-ylindenyl)benzamide

Following the procedure as described in Example 12, and carrying out irrelevant changes, the cyclohexylamine was replaced with 2-ρ-cetinamine and the keto- 5,6-dihydrospiro[benzo[l, 2-b: 5,4-7]difuran_3,3,_十来]_Γ(2Ή)_yl) fluorenyl]benzoic acid substituted 3-[(2'-keto-5,6-dihydro Snail [stupid and like seven: 5,4-b,] difuran-3,3,-吲嗓]-1·(2Ή)-yl)indenyl]benzoic acid, obtaining 4_[(2, keto group) 5 6_Dihydrospiro[benzo[l,2-b : 5,4-b']dioxanyl)indenyl]-indolyl-7-ylmethyl)benzamide %), as a colorless solid: melting point 167_168〇c; ihnmr (3〇〇MHz, CDCI3) δ 7.81-7.73 (m, 2H), 7.43-7.37 (m, 2H), 7.27-7.16 (m, 3H), 143924 -sp-20091127-5 •817- 201020257 7.07-7.00 (m, 2H), 6.99-6.95 (m, 1H), 6.75-6.70 (m, 1H), 6.48-6.40 (m, 3H), 4.99 (ABq, 2H), 4.84 (ABq, 2H), 4.83-4.78 (m, 2H), 4.59-4.50 (m, 2H), 3.09-2.90 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 166.5, 161.9, 161.3, 141.7, 140.6, 139.4, 133.7, 132.6, 128.7, 127.7, 127.5, 126.9, 126.2, 125.3, 124.0, 123.6, 120.0 (2C), 118.8, 109.1, 93.3, 80. 6, 72.4, 57.7, 43.8, 38.8, 29.0; MS (ES+) m/z 509.2 (M + 1). Example 12.39 N-Ethyl-4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-b:5,4-b']difuran-3,3,-吲Synthesis of 哚]-Γ(2Ή)-yl)methyl]benzamide

Replacement of cyclohexanemethylamine with ethylamine (2 Torr in tetrahydrofuran) using 4-[(2^-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4- b·]difuran-3,3,-"51 哚]-1·(2Ή)-yl) fluorenyl]benzoic acid replacement 3-[(2'-keto-5,6-dihydrospiro[benzene And [l,2-b: 5,4-b·]difuran-3,3·-吲哚]-ΐ·(2Ή)-yl)methyl]benzoic acid to obtain N-ethyl-4-[ (2·-keto-5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]difuran-3,3,-W 哚]-1'(2Ή)-yl曱]]benzamide (57%) as a colorless solid: melting point 19〇-191. (:; lU NMR (300 MHz, CDC13) δ 7.79-7.71 (m, 2H), 7.44-7.36 (m , 2H), 7.24-7.15 (m, 2H), 7.08-6.99 (m, 1H), 6.77-6.70 (m, 1H), 6.47 (s, 1H), 6.43 (s, 1H), 6.14-6.04 (m , 1H), 4.99 (ABq, 2H), 4.85 (ABq, 2H), 4.59-4.50 (m, 2H), 3.54-3.43 (m, 2H), 3.09-2.90 (m, 2H), 1.28-1.21 (m , 3H); 13C NMR (75 MHz, CDC13) δ 178.0, 166.8, 161.9, 161.3, 141.8, 139.1, 134.4, 132.6, 143924-sp-20091127-5 -818- 201020257 128.7, 127.5 (2C), 124.0, 123.6 , 120.0, 118.8, 109.1, 93.3, 80.6, 72.4, 57.7, 43.8, 34.9, 29.0, 14.8 MS (ES+) m/z 441.2 (Μ + 1). Example 12.40 N-(2-methoxyethyl)-4-[(2·-keto-5,6-dihydrospiro[benzo[ Synthesis of 1,2-b: 5,4-b,]difuran-3,3'-thoracic]-1'(2Ή)-yl)indolyl]benzamide

Replace cyclohexanemethylamine with 2-methoxyethylamine and use 4-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b· Difuran-3,3·-啕哚]-1,(2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-keto-5,6-diindole][benzo[l, 2-b: 5,4-b,]difuran-3,3,-吲哚]-indole (2Ή)-yl)methyl]benzoic acid to give N-(2-methoxyethyl)-4 -[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b]difuran-3,3'-吲哚]-1'(2Ή)- Phenylamine (49%) as a colorless solid: mp 182-183 ° C; 4 NMR (300 ❿ MHz, CDC13) 5 7.81-7.73 (m, 2H), 7.44-7.37 (m, 2H), 7.23-7.15 (m, 2H), 7.07-7.00 (m, 1H), 6.77-6.70 (m, 1H), 6.56-6.41 (m, 3H), 5.00 (ABq, 2H), 4.85 (ABq, 2H), 4.60-4.51 (m, 2H), 3.68-3.60 (m, 2H), 3.59-3.52 (m, 2H), 3.38 (s, 3H), 3.08-2.94 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ 177.9, 166.9, 161.9, 161.3, 141.8, 139.3, 134.1, 132.6, 128.7, 127.6, 127.5, 124.0, 123.6, 120.0 (2C), 118.8, 109.1, 93.3, 80.6, 72.4, 71.1, 58.8, 57.7, 43.8, 39.7, 29.0; MS (ES+) m/z 471.1 (M + 1). Example 12.41 N-(2-ethoxyethyl)-4-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difur 143924-sp-20091127-5 •819· 201020257 -3-3,3'-p 弓多]-1'(2Ή)-yl) sulfhydryl]

/-ch3 〇 In accordance with the procedure as described in Example 12, and irrelevant changes were made, replacing cyclohexanemethylamine with 2-ethoxyethylamine, and using 4_[(2,_benyl-56-dihydrogen) Snail [benzo[l,2-b: 5,4-b']difuran-3,3,-啕哚]-1,(2Ή)-yl)indolyl]benzoic acid substitution 3-[(2· -keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-indole]-1'(2Ή)-yl) fluorenyl ]benzoic acid 'obtained N-(2-ethoxyethyl)-4-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-7'] Difuran-3,3,-anthracene-1,(2Ή)-yl)methyl]benzamide (48%) 'is a colorless solid. ·M.p. 84-85 ° C; 1H NMR (300 MHz, CDC13) δ 7.80-7.73 (m, 2Η), 7.44-7.38 (m, 2H), 7.23-7.15 (m, 2H), 7.07-7.00 (m, 1H), 6.11-6.11 (m, 1H), 6.58- 6.50 (m, 1H), 6.47 (s, 1H), 6.43 (s, 1H), 5.00 (ABq, 2H), 4.85 (ABq, 2H), 4.60-4.50 (m, 2H), 3.68-3.48 (m, 6H), 3.11-2.91 (m, 2H), 1.21 (t, J = 7.0, Hz3H); 13 C NMR (75 MHz, CDC13) δ 177.9,166.9,161.8,161.3,141.8,139.2,134.2, 132.6, 128.7 , 127.6, 127.5, 124.0, 123.6, 120.0 (2C), 118.8, 109.1, 93.2, 80.6, 72.4 , 68.9, 66.5, 57.7, 43.8, 39.8, 29.0, 15.1; MS (ES+) m/z 485.1 (M+l). Example 12.42 N-Cyclobutyl-4-[(2-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3-indole] Synthesis of -1 (2H&gt;yl) fluorenyl]benzamide 143924-SP-20091127-5 •820· 201020257 α Ο ~ 0 Follow the procedure as described in Example 12, and perform irrelevant changes, use Cyclobutylamine hydrochloride replaces cyclohexanemethylamine and uses 4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Difuran-3,3'-indole]-indole (2Ή)-yl) fluorenyl] oxalic acid substituted 3-[(2,-keto-5,6-dihydrospiro[benzo[1,2] VII:5,4,7,]difuran-3,3·-^ 哚Η'(2Ή)-yl)methyl]benzoic acid, obtained Ν-cyclobutyl-4-[(2-keto-5, 6-dihydrospiro[{,2,7,5,4,7]difuran-3,3-indolyl]-1(2Η)-yl)indolyl]benzamide (25%) ' is colorless solid: melting point &gt; 250 ° C; NMR (300 MHz, CDC13) δ 8.61-8.55 (m, 1H), 7.85-7.78 (m, 2H), 7.46-7.38 (m, 2H), 7.29-7.15 (m, 2H), 7.07-6.93 (m, 2H), 6.46 (s, 1H), 6.44 (s, 1H), 5.08-4.90 (m, 2H), 4.80 (ABq, 2H), 4.55-4.46 (m , 2H), 4.46-4.31 (m, 1H), 3.05-2.91 (m, 2H), 2.26-2.12 (m, 2H), 2.12-1.95 (m, 2H), 1.72-1.60 (m, 2H); 13C NMR (75 MHz, CDC13) &lt;5 177.1, 164.9, 161.1, 160.7, 142.0, 139.2, 133.7, 132.0, 128.6, φ 127.7, 126.9, 123.7, 123.1, 120.3, 119.9, 118.8, 109.3, 92.4, 79.8, 72.0, 56.9, 44.4, 42.8, 30.0, 28.3, 14.6; MS (ES+) m/z 467.1 (M+l). Example 12.43 4-[(2'-ketone) -5,6-dihydrospiro[benzo[1,2:7:5,4-1)|]difuran-3,3,-anthracene-1,(2,11)-yl)methyl Synthesis of Ν-1,3μ*pyrazol-2-ylbenzamide

143924-sp-20091127-5 -821 · 201020257 Following the procedure as described in Example 12, and applying an insignificant change, replace the cyclohexane methylamine with 2-amino hydrazine and use 4_[(2,_ Keto group _5,6-dihydrospiro[benzo[l,2-b: 5,47']difuran_3,3,,哚]-1,(2Ή)-yl)indolyl]phenylhydrazine Acid replacement of 3-[(2'--yl-5,6-dihydrospiro[benzo-like:7:4-b1]difuran-3,3,-,5丨哚]-Γ(2Ή)- ))methyl]benzoic acid 'obtained 4_[(2, keto- 5,6-dihydrospiro[benzopyrene: 5,4-7]] bismuth-3,3'-吲哚] -1, (2,H)-yl)methyl]-Nl, 3-pyrimidine. -2--2-ylbenzamide (46%) ' is a colorless solid: melting point &gt; 25 〇t; iHNMR (3 〇〇 MHz CDCl3) δ 12.63 (s, 1H), 8.11-8.05 (m, 2H), 7.57-7.47 (m, 3H), 7.31-7.18 (m, 3H), 7.08-6.98 (m, 2H), 6.49 (s, 1H), 6.44 (s, 1H), 5.12-4.96 (m, 2H), 4.82 (ABq, ® 2H), 4.58-4.43 (m, 2H), 3, 08-2.89 (m, 2H); MS (ES+) m/z 496.1 (M + 1). Example 12.44 N-(3-Fluoro-2-methylphenyl)_4_[(;2,-keto-5,6-dihydrospiro[benzo[1,2-b: 5,4-b' Synthesis of diterpene-3,3'-吲哚]-Γ(2,Η)-yl)methyl]benzamide

Replacement of cyclohexane decylamine with 3-hydroxy-2-mercaptoaniline and use 4_[(2,__yl-5,6-dihydrospiro[benzo[1,2-7:5,4-b] ,]difuran-3,3,-吲哚]-Γ(2Ή)-yl)methyl]benzoic acid substituted 3-[(2'-keto-5,6-dihydrospiro[benzo[l, 2-b: 5,4,7,]difuran-3,3,-4嗓]-Γ(2Ή)-yl)indenyl]benzoic acid, obtaining N_(3-fluoro-2-indolinylphenyl) )_4_ [(2·-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-7,]difuran-3,3,-啕哚]-1, (2Ή) -yl)methyl]benzamide (35%) as a colorless solid: m.p. 143 - 144 °C; iHNMR (300 MHz, CDC13) δ 7.91-7.84 (m, 2 Η), 7.74-7.64 (m, 2H ), 7.52-7.45 (m, 143924-sp-20091127-5 -822-

(S 201020257 2H), 7.29-7.17 (m, 3H), 7.10-7.02 (m, 1H), 6.96-6.87 (m, 1H), 6.80-6.74 (m, 1H), 6.49 (s, 1H), 6.44 (s, 1H), 5.04 (ABq, 2H), 4.85 (ABq, 2H), 4.60-4.51 (m, 2H), 3.10-2.91 (m, 2H), 2.23 (d, J = 1.51 Hz, 3H); MS (ES+) m/z 521.0 (M+l). Example 12.45

N-(2-ethylbutyl)-4-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3, Synthesis of 3W丨哚]-Γ(2Ή)-yl) benzyl]benzamide

Following the procedure as described in Example 12, and carrying out irrelevant changes, replacing cyclohexane decylamine with 2-ethyl-n-butylamine and using 4-[(2·-keto-5,6) -Dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-1·(2Ή&gt;yl)methyl]

Benzoic acid substitution 3-[(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3·-吲哚]- Γ(2Ή)-yl)methyl]benzoic acid, obtained Ν-(2-ethylbutyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2- b: 5,4-b]difuran-3,3'-indole]-indole (2Ή)-yl)methyl] acesulfame (60%) as a colorless solid: m.p. 211-213. iHNMR (300MHz, CDC13) δ 7.78-7.70 (m, 2Η), 7.44-7.37 (m, 2H), 7.24-7.15 (m, 2H), 7.08- 7.00 (m, 1H), 6.77-6.71 (m, 1H) ), 6.47 (s, 1H), 6.44 (s, 1H), 6.08-5.99 (m, 1H), 4.99 (ABq, 2H), 4.85 (ABq, 2H), 4.59-4.50 (m, 2H), 3.44- 3.36 (m, 2H), 3.10-2.91 (m, 2H), 1.55-1.30 (m, 5H), 0.97-0.87 (m, 6H); MS (ES+) m/z 497.0 (M + 1). Example 12.46 2-(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-b,]dioxan-3,3,-啕哚]-1, ( 2Ή)- 143924-sp-20091127-5 -823 - 201020257 base) Synthesis of acetamide

(2, keto-5,6-dihydrospiro[benzo[[:5,4_b,] two bite m ten]_ Γ(2Ή)·yl)acetic acid (〇25g, 〇74mmol Ear), triethylamine (〇5 ml), ammonia in ammonia (0.5 Μ, 4.5 ml, 2.3 mmol) in a stirred solution of acetonitrile (1 mL), hexafluorophosphate 2_(7 Nitrogen-1 Ηbenzotriazolyl)_ 1,1'3,3-tetramethylguanidine (0.33 g, 〇9 mmol). The solution was stirred at ambient temperature for 18 hours and then concentrated to dryness in vacuo. The residue was dissolved in ethyl acetate (50 mL) andEtOAcEtOAcEtOAc The ethyl acetate layer was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to dryness. Recrystallization from diethyl ether (25 ml) in a water bath on a Branson ultrasonic bench gave 2-(2,-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4 VII']difuran-3,3,-吲哚]-Γ(2Ή)-yl)acetamide (0.06 g,

23%), as a colorless solid: iH NMR (300 MHz, DMSO-d6) δ 7.66 (s, 1 Η), 7.29-7.21 (m, 2 Η), 7.10 (d, J = 6.5 Hz, 1H), 7.03-6.90 (m, 2H), 6.55 (s, 1H), 6.36 (s, 1H), 4.72 (ABq, 2H), 4.53-4.38 (m, 1H), 4.29 (ABq, 2H), 2.92 (t, J = 8.6 Hz, 2H) ; MS (ES+) mJz 337.1 (M + 1), 359.1 (M + 23) = Example 12.47 N-(4-ethylphenyl)-2-(2·-keto-5,6- Synthesis of dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-indole]-indole (2Ή)-yl)acetamide 143924-sp-20091127- 5 -824-

201020257

According to the procedure as described in Example 12.46, and irrelevant changes were made, the ammonia in the dioxane was replaced with 4-ethylaminobenzene to obtain the group (4) ethylphenyl)-2-(2'-keto). -5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxin-3,3,-p5丨嗓]-1'(2Ή)-yl)acetamide (69%) as colorless solid: 1H NMR (300 MHz, DMSO-d6) &lt;5 10.25 (s, 1H), 7.45 (d, J = 8.4 Hz, 2H), 7.26 (dd, J = 7.3, 7.3 Hz, 1H), 7.16-7.09 (m, 3H), 7.08-6.95 (m, 2H), 6.56 (s, 1H), 6.38 (s, 1H), 4.73 (ABq, 2H), 4.56 (ABq, 2H) , 4.50-4.41 (m, 2H), 2.94 (t, J = 8.6 Hz, 2H), 2.53 (q, J = 7.5 Hz, 2H), 1.11 (t, J = 7.6 Hz, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ ΙΊΊ.1, 165.3, 161.6, 161.0, 143.2, 139.4, 136.8, 132.6, 129.1, 128.5, 123.9, 123.4, 121.2, 120.3, 119.7, 109.5, 92.9, 80.2, 72.6, 57.3, 43.5 , 28.8, 28.0, 16.2; MS (ES+) m/z 441.1 (M + 1) 〇 Example 12.48 N,N-Diethyl-2-(2,-keto-5,6-dihydrospiro[Benzene Synthesis of [l,2-b : 5,4-b,]difuran-3,3,- 吲哚]-Γ(2Ή)-yl)acetamide

According to the procedure as described in Example 12.46, and irrelevant changes were made, the ammonia in the dioxane was replaced with diethylamine to obtain hydrazine, Ν-diethyl-2-(2·-keto-5, 6-Dihydrospiro[benzo[l,2-b:5,4-b']difuran_3,3'_thirsty' (2'Η)-yl)B 143924-sp-20091127-5 -825 - 201020257 decylamine (54%) as colorless solid: iHNMRGOOMHz 'DMSO-de) 5 7.28-7.21 (m, 1H), 7.10 (d, J = 7.3 Hz, 1H), 6.98 (dd, J = 7.5 , 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.57 (s, 1H), 6.37 (s, 1H), 4.76-4.66 (m, 2H), 4.60 (ABq, 2H), 4.50 -4.41 (m, 2H), 3.46-3.36 (m, 2H), 3.31-3.20 (m, 2H), 2.93 (t, J = 8.6 Hz, 2H), 1.19 (t, J = 7.1 Hz, 3H), 1.00 (t, J = 7.1 Hz, 3H); 13 C NMR (75 MHz, DMSO-d6) &lt;5 177.8, 165.0, 161.5, 160.9, 143.4, 132.7, 129.0, 123.8, 123.2, 121.3, 120.2, 119.9, 109.6, 92.8, 80.2, 72.5, 57.3, 41.7, 41.0, 28.8, 14.6, 13.5; MS (ES+) m/z 393.1 (M + 1). Example 12.49 N-(3,3-Dimercaptobutyl)-2-(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,] Synthesis of Furan-3,3'-吲哚]-Γ(2Ή)-yl)acetamide

(2'-Mercapto-5,6-dihydrospiro[benzo-like seven:5,4_b,]difuran_3 3·_^哚]_ 1 (2Ή)-yl)acetic acid (〇·25g , 〇 '74 millimoles), isobutyl phthalate (〇η ml, 0.81 mmol) 'Ν-methylmorpholine (0.09 ml, 〇81 mmol) in di-methane (1〇 3,3-Dimethylbutylamine (0.11 g, I·1 mmol) was added to the stirred solution in ML). The solution was stirred at ambient temperature for 16 hours, diluted with di-methane (EtOAc) and washed with EtOAc (2 EtOAc). The organic layer was dried over magnesium sulfate, filtered, and concentrated in vacuo to dry. The residue was purified by flash chromatography using ethyl acetate in hexane to 50% gradient to give Ν((3,3 dimethyl yl) W2, decyl 6 diazepine [benzo [1'2-b · 5,4-b']difuran_3,3,_ρ5丨哚]_Γ(2Ή)yl)acetamide (〇13 g, 143924-sp-20091127-5 201020257 41%) , as colorless solid: mp 161-163 ° C; iHNMRGOOMHtDMSO-cU δ 8.14 (dd, J = 5.4, 5.4 Hz, 1H), 7.25 (dd, J = 7.6, 7.6 Hz, 1H), 7.11 (d, J = 6.9 Hz, 1H), 7.03-6.95 (m, 1H), 6.90 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.37 (s, 1H), 4.71 (ABq, 2H), 4.51- 4.40 (m, 2H), 4.38-4.20 (m, 2H), 3.12-3.01 (m, 2H), 2.93 (t, J = 8.6 Hz, 2H), 1.37-1.27 (m, 2H), 0.85 (s, 9H) ; 13 C NMR (75 MHz, DMSO-c^) δ 177.6, 166.3, 161.5, 160.9, 143.1, 132.7, 129.0, 123.8, 123.3, 121,3, 120.2, 119.8, 109.4, 92.8, 80.2, 72.5, 57.3, 43.2, 43.0, 35.9, 30.0, 29.7, 28.8; MS (ES+) m/z 421.2 (M + 1). Example 12.50 N-[3-(l-Mercaptoethoxy)propyl]-2-(2'-keto-5,6-dihydrospiro[benzo[1,2-b: 5,4- Synthesis of b']difuran-3,3'-吲哚]-fluorene (2Ή)-yl)acetamide

According to the procedure as described in Example 12.49, and irrelevant changes were made, 3,3-dimethylbutylamine was replaced with 3-isopropoxypropylamine to obtain N-[3-(l-methylethoxy). )propyl]-2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3 吲哚]-Γ(2Ή) -yl) acetamidine (22%) as colorless solid: m.p. 149-151 °C; 1H NMR (300 MHz, DMSO-d6)5 8.18 (dd, J = 5.4, 5.4 Hz, 1H), 7.25 (dd , J = 7.7, 7.7 Hz, 1H), 7.11 (d, J = 6.9 Hz, 1H), 6.99 (dd, J = 7.5, 7.5 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.37 (s, 1H), 4.71 (dd, J = 21.2, 9.3 Hz, 1H), 4.50-4.41 (m, 1H), 4.31 (ABq, 1H), 3.52-3.39 (m, 1H) ), 3.36-3.30 (m, 1H), 3.11 (dd, J = 12.8, 6.7 Hz, 1H), 2.93 (t, J = 8.5 Hz, 1H), 1.65-1.52 (m, 1H), 1.02 (d, J = 6.1 Hz, 1H) ; 13 C NMR (75 MHz, DMSO-^) δ 177.6, 143924-sp-20091127-5 -827- 201020257 166.5, 161.5, 160.9, 143.1, 132.1, 132.7, 129.0, 123·8 , 123.3, 121.3, 120.2,

MS (ES+) m/z 437.2 (M+l) 〇 Example 12.51 2-(2·-keto-5,6-dihydrospiro[benzo[1,2:7:5,4-b,]; Synthesis of furan-3,3,-called 丨哚]-Γ(2Ή)-yl)-Ν-propylacetamide

Following the procedure as described in Example 12.49, and carrying out irrelevant changes, replacing 3,3-dimethylbutylamine with propylamine afforded 2-(2·-keto-5,6-dioxaspiro[benzo [l,2-b : 5,4-b]difuran-3,3'-indole]-indole (2Ή)-yl)-indole-propylacetamide (44%) as a colorless solid: melting point 207-209°C; NMR (300 MHz, DMSO-d6) δ 8.19 (dd, J = 5.5, 5.5 Hz, 1H), 7.25 (dd, J = 7.7, 7.7 Hz, 1H), 7.11 (d, J = 6.7 Hz, 1H), 6.99 (dd, J = 7.2, 7.2 Hz, 1H), 6.91 (d, J = 7.8 Hz, 1H), 6.53 (s, 1H), 6.37 (s, 1H), 4.72 (ABq, 2H), 4.50-4.41 (m, 2H), 4.32 (ABq, 2H), 3.03 (dd, J = 12.9, 6.7 Hz, 2H), 2.93 (t, J = 8.6 Hz, 2H), 1.49-1.30 (m , 2H), 0.82 (t, J = 7.39 Hz, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.6, 166.4, 161.5, 160.9, 143.2, 132.7, 129.0, 123.8, 123.3, 121.3, 120.2, 119.8 , 109.4, 92.8, 80.2, 72.5, 57.3, 43.0, 41.0, 28.8, 22.8, 11.8; MS (ES+) m/z 379.1 (M + 1). Example 12.52 N-Methyl-2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-&lt; Synthesis of 哚]-Γ(2Ή)-yl)-N-phenylacetamide 143924-sp-20091127-5 -828- 201020257

According to the procedure as described in Example 12.49, and irrelevant changes were made, N-methylaniline was used to replace 3,3-dimethylbutylamine to obtain N-methyl-2_(2,-keto-5, 6-Dihydrospiro[benzo[i,2-b : 5,4-b']difuran-3,3'-啕哚]-1,(2Ή)-yl)-N-phenyl-ethylidene Amine (27%) as colorless solid: m.p. s. s. s. s. s. s. s. s. s. , 7.09 (d, J = 6.7 Hz, 1H), 7.02-6.93 (m, 1H), 6.54 (s, 1H), 6.36 (s, 1H), 4.73-4.61 (m, 2H), 4.50-4.40 (m , 2H), 4.19 (ABq, 2H), 3.18 (br s, 3H), 2.92 (dd, J = 8.5, 8.5 Hz, 2H) ; 13 C NMR (75 MHz, DMSO-d6) &lt;5 177.5,165.9 , 161.5, 160.9, 143.1, 132.6, 130.5, 128.9, 127.9, 123.8, 123.3, 121.3, 120.2, 119.8, 109.7' 92.8, 80.0, 72.5, 57.2, 42.4, 37.7, 28.8 ; MS (ES+) m/z 427.1 ( M + 1) 〇 Example 12.53 ❹ 2(2,5-Dimethylphenyl)-2-(2'-keto-5,6-dihydrospiro[benzo[1,2:7:5,4- 1) Synthesis of ']disyl-3,吲哚]-Γ(2Ή)-yl)acetamide

According to the procedure as described in Example 12.49, and irrelevant changes were made, 3,3-dimercaptobutylamine was replaced with 2,5-diphenylaniline to obtain ν_(2,5-dimercaptophenyl)- 2-(2,-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-anthracene; μ-829- 143924- Sp-20091127-5 201020257 Γ(2Ή)-yl) acetamidine (63%) as colorless solid: m.p. 250-252°C; iHNMR (300 MHz, DMSO-d6) δ 9.63 (s, 1H), 7.33 -7.25 (m, 1H), 7.21-6.97 (m, 6H), 6.91-6.85 (m, 1H), 6.53 (s, 1H), 6.38 (s, 1H), 4.74 (dd, J = 23.9, 9.4 Hz , 2H), 4.60 (dd, J = 29.3, 17.3 Hz, 2H), 4.49-4.41 (m, 2H), 2.92 (dd, J = 8.6, 8.6 Hz, 2H), 2.20 (s, 3H), 2.14 ( s, 3H) ; 13C NMR (75 MHz, DMSO-dg) δ 111.7, 165.7, 161.6, 160.9, 143.1, 136.0, 135.5, 132.8, 130.7, 129.1, 126.6, 125.9, 123.9, 123.4, 121.3, 120.2, 119.7, 109.4, 92.8, 80.2, 72.5, 57.3, 43.3, 28.8, 21.0, 17.9; MS (ES+) m/z 441.2 (M + 1). Example 12.54 N-(2,4-Dimercaptophenyl)-2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b·] Synthesis of Furan-3,3'-吲哚]-Γ(2Ή)-yl)acetamide

According to the procedure as described in Example 12-9, and irrelevant changes were made, 3,3-dimethylbutylamine was replaced with 2,4-dimethylaniline to obtain Ν-(2,4-dimethylphenyl). -2-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-&lt;*5丨哚]- 1'(2Ή)-yl)acetamide (67%) as colorless solid: mp 277-279t; 1H NMR (300 MHz, DMSO-d6) (5 9.62 (s, 1 Η), 7.28 (dd, J = 7.6, 7.6 Hz, 1Η), 7.21 (d, J = 8.0 Hz, H), 7.12 (d, J = 6.9 Hz, 1H), 7.08-6.89 (m, 4H), 6.53 (s, 1H), 6.38 ( s, 1H), 4.74 (ABq, 2H), 4.59 (m, 2H), 4.49-4.41 (m, 2H), 2.91 (dd, J = 8.6, 8.6 Hz, 2H), 2.21 (s, 3H), 2.15 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.7, 165.7, 161.6, 160.9, 143.1, 135.1, 133.6, 132.8, 132.3, 131.4, 129.0, 128.6, 127.0, 125.5, 123.9, 121.3, 120.2, 119.7, 109.4, 92.8, 80.2, 72.5, 57.4, 143924-SD-20091127-5 -830- 201020257 55.4, 43.3, 28.8, 20.9, 18·3 ; MS (ES+) m/z 441.2 (Μ + 1) Example 12.55 Ν-(2,3-Dimethylphenyl)-2-(2:keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b·]吱喃-3,3W丨哚]- Synthesis of 1'(2Ή)-yl)acetamide

According to the procedure as described in Example 12.49, and irrelevant changes were made, 3,3-dimercaptobutylamine was replaced with 2,3-dimethylaniline to obtain Ν-(2,3-dimercaptophenyl). -2-(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']di-p-β-South-3,3'-p?丨ρ ]-Γ(2Ή)-yl)acetamide (55%) as a colorless solid: mp 251-253. NMR; WNMR (300 MHz, DMSO-d6) δ 9.76 (s, 1 Η), 7.29 (dd, J = 7.4, 7.4 Hz, 1H), 7.15-6.96 (m, 6H), 6.52 (s, 1H), 6.37 (s, 1H), 4.74 (ABq, 2H), 4.60 (ABq, 2H), 4.49-4.40 (m, 2H), 2.91 (dd, J = 8.6, 8.6 Hz, 2H), 2.21 (s, 3H), 2.06 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.7, 165.8, 161.8, 160.9, 143.1, 137.6, 136.0, 132.8, 131.8, 129.0, 127.7, 125.7, 124.0, 123.4, 121.3, 120.2, 119.7, 109.4, 92.8, 80.2, 72.5, 57.3, 43.3, 28.8, 20.6, 14.5; MS (ES+) m/z 441.2 (M + 1). Example 12.56 N-(2,6-Dimethylphenyl)-2-(2·-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Synthesis of furan-3,3W丨哚]-Γ(2Ή)-yl)acetamide

-831- 143924-sp-20091127-5

201020257 Following the procedure as described in Example 12.49, and carrying out irrelevant changes, replacing 3,3-dimercaptobutylamine with 2,6-diphenylaniline to obtain N-(2,6-dimethylphenyl) )-2-(2·-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b·]difuran-3,3·- 哚 哚]-1·( 2Ή)-yl)acetamide (67%) as colorless solid: mp 261-262 ° C; 1H NMR (300 MHz, DMSO-d6) &lt;5 9.66 (s, 1H), 7.30 (dd, J = 7.7, 7.7 Hz, 1H), 7.16-6.98 (m, 6H), 6.51 (s, 1H), 6.37 (s, 1H), 4.75 (ABq, 2H), 4.67-4.52 (m, 2H), 4.49-4.40 (m, 2H), 2.90 (dd, J = 8.6, 8.6 Hz, 2H), 2.12 (s, 6H); 13 C NMR (75 MHz, DMSO-d6) δ 177.7, 165.4, 161.5, 160.9, 143.0, 135.7 , 135.0, 132.9, 128.9, 128.2, 127.1, 123.9, 123.4, 121.3, 120.2, 119.7, 109.3, 92.8, 80.2, 72.5, 57.4, 43.0, 28.8, 18.6, 15.6; MS (ES+) ni/z 441.2 (M + 1). Example 12.57 N-Methyl-5-[(2·-oxaspiro[吱,[2,3_f][i,3]benzodioxolene-7,3,_p?| 嗓]-Γ( Synthesis of 2Ή)-yl)mercapto]-2-(trifluoromethyl)pyran-3-carboxydecylamine

H3ct, &quot; cf3 Follow the procedure as described in Example 12.49, and perform irrelevant changes, using methylamine hydrochloride to replace 3,3-dimercaptobutylamine, using 5_[(2,_ oxo[rho] Furano[2'3-f][l,3]benzodioxanthene_7 31_吲哚] r(2,H)yl)methyl]_2(trifluoromethyl)-pyran 3-carboxylic acid substitution (2'-keto-5,6-dihydrospiro[benzo[[7:5,4-7]]difuran-3,3'-吲哚]-1' (2Ή&gt; ) Acetic acid, which gives N-based _5 [(2, oxo[furo[2,3-f][l,3] benzodioxolanes _7 3,, 哚]], (10) yl) Base]_2 (trifluoromethyl) anthraquinone-3-treazone (96%), colorless solid: melting point 2〇2 2〇3t (B shouting / 143924-sp-20091127-5 •832· 201020257 burned 4 NMR (300 MHz, CDC13) (5 7.31-7.27 (m, 2H), 7.19-7.17 (m, 1H), 7.10-7.05 (m, 1H), 6.95-6.92 (m, 1H), 6.62 ( s, 1H), 6.49 (s, 1H), 6.09 (s, 1H), 5.94 (br s, 1H), 5.85-5.84 (m, 2H), 5.03-4.85 (m, 3H), 4.67-4.64 (m , 1H), 2.92 (d, J = 3.0 Hz, 3H); MS (ES+) m/z 487.3 (M + 1). Example 12.58 5-[(2'-Oxospiro[吱,[2,3- f][l,3]benzodioxan _7,3, _ steep indole] _i, (2, h) - yl) methyl] -2- (trifluoromethyl) squeak thiopyran _3- Synthesis of 2carboxamide

Follow the procedure as described in Example 12.49 and perform irrelevant changes by replacing 3,3-dimethylbutylamine with 7N ammonia solution in decyl alcohol and using 5_[(2,_ oxo[ [2,3-f][l,3]benzodioxanthene_7,3'-吲哚]-1,(2Ή)-yl)methyl]-2-(trifluoromethyl)anthracene Replacement of carboxy-3-carboxylic acid (2,-keto-5,6-dihydrospiro[benzoxanthene[Hb:5,4_b']difuran_3,3'-called | 哚]-1, (2Ή --)acetic acid to obtain 5-[(2,-oxaspiro[rho][2,3-f][l,3]benzodioxolene-7,3·-吲嗓]-Γ (2Ή&gt;-based) fluorenyl-2-(dimethyl)c-butyl-3-carboxamide (86%) as colorless solid: mp 172-174 C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) 6 7.32-7.27 (m, 1H), 7.20-7.17 (m, 1H), 7.11-7.06 (m, 1H), 6.97-6.94 (m, 1H), 6.70 (s, 1H), 6.49 (s, 1H), 6.09-6.02 (m, 3H), 5.83 (ABq, 2H), 5.85-5.84 (m, 2H), 5.03- 4.85 (m, 3H), 4.67-4.64 (m, 1H); MS (ES+) m/z 473.2 (M + 1). Example 12.59 N,N-Dimethyl-5-[(2·-oxaspiro[c-buto[2,3-f][l,3]benzene And dioxolene 143924-sp^20091127-5 -833- 201020257 W哚]-Γ(2Ή)-based) Yl] _2- (trifluoromethyl) -3- slow squeak pyran-amine of acyl

%-N, CH3CF3 Follow the procedure as described in Example 12.49, and perform irrelevant changes, replace 3,3-dimethylbutylamine with diamine hydrochloride, and use 5-[(2'-oxygen) Snail [c-buto[2,3-f][l,3]benzodioxanthene-7,3'-吲哚]-indole (2Ή)-yl) fluorenyl; 1_2_(trifluoromethyl Substituted furan-3-carboxylic acid (2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,47-difuran-3,3'-峋哚]-Γ (2Ή)-yl)acetic acid, obtained Ν,Ν-dimethyl-5-[(2,-oxaspiro[吱,[2,3-f][l,3] benzodioxolan] 7,3'-啕哚]-Γ(2Ή)-yl)methyl]_2·(trifluoromethyl)anthran-3-carboxamide (32%) as colorless solid: mp. 96-98. (ethyl acetate / hexane); NMR (300 MHz, CDC13) (5 7.32-7.27 (m, 1H), 7.19-7.17 (m, 1H), 7.10-7.05 (m, 1H), 6.96-6.94 (m , 1H), 6.50 (s, 1H), 6.40 (s, 1H), 6.09 (s, 1H), 5.86-5.85 (m, 2H), 5.05-4.87 (m, 3H), 4.68-4.65 (m, 1H) MS (ES+) m/z 501.3 (M + 1). Example 12.60 4-[(2'-keto-2,3-dihydrospiro[furo[2,3-g][l,4] Synthesis of benzodioxanthene 吲哚]-Γ(2Ή)-yl) fluorenyl]benzamide

143924-sp-20091127-5 - 834- 201020257 in 4-[(2,-keto-2,3-dihydrospiro[2,3.,4]benzodioxanthene-8 , 34哚Η, (2Ή)-yl)methyl]benzoic acid (〇.43 g, i 〇〇 millimol) in a solution of dichloromethane, adding chlorinated grass 醯 (〇 2 ml, 24 Millol) followed by N,N-dimercaptocaramine (1 drop). The reaction mixture was stirred at ambient temperature for 5 h and concentrated in vacuo. The residue was dissolved in di-methane (1 mL) and then taken to a &lt;RTI ID=0.0&gt;&gt; The reaction mixture was stirred at ambient temperature for 18 h and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate to give 4-[(2-keto-2,3-diopter) [吱,[2,3-g][l, 4] benzodioxanthene-8,3·-啕哚]-1·(2Ή)-yl)methyl]benzamide (0.15 g, 35%): mp 236-238. (:(ethyl acetate); 4 NMR (300 MHz, DMSOO 5 7.93-7.80 (m, 3 Η), 7.39-7.33 (m, 3H), 7.25-7.14 (m, 2H), 7.02-6.94 (m, 2H ), 6.50 (s, 1H), 6.08 (s, 1H), 4.94 (ABq, 2H), 4.72 (ABq, 2H), 4.16-4.07 (m, 4H) ; 13 C NMR (75 MHz, DMSO-d6) δ 111.2, 167.9, 155.2, 144.6, 142.5, 140.0, 138.3, 134.0, 132.1, 129.2, 128.3, 127.4, 124.1, 123.6, 121.6, 111.4, 109.8, 99.3, 79.9, 64.6, 64.0, 57.2, 43.2 ; MS (ES+ m/z 429.0 (M + 1). ❹ Example 12.61 3-[(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzoic Synthesis of Oxygen-ene-ene-8,3'-吲哚]-1'(2Ή)-yl)indolyl]benzamide

3-[(2'-keto-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene 143924-sp-20091127-5 -835 - 201020257 _8,3'4 Noise H'(2'H)-yl)methyl]benzoic acid (1.04 g ' 2.42 mmol) in anhydrous chloroform (50 ml), add gasified grass醯 (0.50 ml, 5 7 mmol) with anhydrous hydrazine, hydrazine-dihydrazinamide (2 drops). The reaction mixture was stirred at ambient temperature for 2 h then concentrated in vacuo. The residue was dissolved in dry EtOAc (3 mL) EtOAc (EtOAc)EtOAc. 2 hours at ambient temperature, filtration, and concentration in vacuo. The residue was purified by column chromatography eluting with acetone/di-methane (1/9), then recrystallized from di-methane/diethyl ether. 3-[(2,-keto-2,3-dihydrospiro[,,[2,3-g][i,4] Φ benzodioxanthene-8,3·-吲哚] - Γ(2Ή)-yl)methyl]benzoguanamine (1.03 g, 99%) as colorless solid: m.p.: 130-135 ° C (di-hexane/ethyl ether); 1hnmr (300 MHz, CDC13) (5 7.81 (s, 1H), 7.71-7.69 (m, 1H), 7.48-7.39 (m, 2H), 7.21-7.15 (m, 2H), 7.04-6.99 (m, 1H), 6.76-6.74 (m, 1H) , 6.49 (s, 1H), 6.23 (s, 1H), 6.10 (br s, 1H), 5.71 (br s, 1H), 5.14-5.09 (m, 1H), 4.95-4.81 (m, 2H), 4.67 -4.64 (m, 1H), 4.19-4.08 (m, 4H); 13C NMR (75 MHz, CDC13) &lt;5 177.7, 168.7, 155.3, 144.7, 141.8, 138.4, 136.5, 134.0, 132.1, 130.8, 129.4, References 128.9, 126.8, 126.5, 124.0, 123.7, 120. 9, 111.4, 109.2, 99.5, 80.0, 64.5, 63.9, 58.1, 43.8; MS (ES+) m/z 428.8 (M + l). Example 12.62 N,N-dimercapto-3-[(2'-one Base-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-Γ(2Ή)-yl)曱Synthesis of benzoylamine 143924-sp-20091127-5 -836- 201020257

3-[(2·-keto-2,3-dihydrospiro[,,[2,3-g][l,4]benzodioxanthene-8,3% 哚]- Add chlorinated grass mash (0.25 ml, 2.9 mmol) to a solution of hydrazine (2 Ή)-yl)methyl]benzoic acid (〇.5 g, 1.16 mmol) in anhydrous gas (25 ml) ) with anhydrous hydrazine, hydrazine-dimethylformamide (1 drop). The reaction mixture was stirred at ambient temperature for 2 hours and concentrated in vacuo. The residue was dissolved in dry dioxane (10 mL) and EtOAc (EtOAc m. Milliol) in a cooled (0 ° C) solution in anhydrous dichloromethane (10 mL). The reaction mixture was stirred at 0 &lt;0&gt;C for 45 min and at ambient temperature for 3 h, filtered and concentrated in vacuo. The residue is recrystallized to give N,N-dimethyl-3-[(2'-keto-2,3-dihydrospiro[furo[2,31][1,4]benzo) Dioxetene 哚]-Γ(2Ή)-yl)methyl]benzamide (0.04 g, 8%), light brown _ solid: melting point: 90-96 ° C (hexane); 1H NMR (300 MHz, CDC13) (5 7.37-7.34 (m, 4H), 7.21-7.14 (m, 2H), 7.04-7.00 (m, 1H), 6.77-6.75 (m, 1H), 6.49 (s, 1H) , 6.19 (s, 1H), 5.08-5.03 (m, 1H), 4.93-4.82 (m, 2H), 4.67-4.64 (m, 1H), 4.20-4.09 (m, 4H), 3.08 (s, 3H) , 2.90 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.6, 171.1, 155.3, 144.7, 141.9, 138.3, 137.0, 136.0, 132.1, 129.1, 128.9, 128.3, 126.6, 126.0, 124.0, 123.6, 120.9, 11L5, 109.2, 99.5, 80.2, 64.5, 63.9, 58.0, 43.9, 39.6, 35.3; MS (ES+) m/z 456.8 (M + 1). Example 12.63 143924-sp-20091127-5 - 837- 201020257 N -Methyl-2-[(2'-keto-2,3-dihydrospiro[indolyl[2 3_g][1,4]benzodioxanthene-8,3'-4丨嗓) Synthesis of Γ-(2Ή&gt;-based) fluorenyl azide _3_carboxamide

In a 50 ml round bottom flask, 'filled with 2_[(2, keto-2,3_dioxaspiro[2'3-g][l,4]benzodioxene _8 , 3'_峋哚]-like ugly)-yl)methyl azidine-3-carboxylic acid (0.43 g ' 1. 〇 millimolar), methylamine hydrochloride (〇 14 g, 2 〇 millimol ), ❹ 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (〇26 g, 丄4 mmol), 1-hydroxybenzotriazole (0.20 g) , 1.5 millimolar), N-mercapto rifampin (0.4 ml '3.6 mmol) and N,N-dimethylformamide (7 ml). The reaction mixture was stirred under nitrogen at ambient temperature for 2 hrs and poured into water (2 mL). The solid was collected by filtration, washed with water, dried, and purified by column chromatography, and eluted with ethyl acetate in a mixture of 〇% to 5 〇% in methane methane to give N-methyl-2-[ (2,-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-Γ(2Ή )-yl)methyl azaindole-3-carboxamide (0.41 g, ® 92%) as an off-white solid: iHNMR (300 MHz, CDC13) δ 8.43 (d, J = 4.8 Hz, 1H), 7.85 (d , J = 7.7 Hz, 1H), 7.36 (dd, J = 7.5, 5.0 Hz, 1H), 7.20-7.07 (m, 2H), 6.95 (t, J = 7.5, 1H), 6.81 (d, J = 7.8 Hz, 1H), 6.46 (d, J = 1.2 Hz, 1H), 6.43 (d, J = 1.2 Hz, 1H), 5.16 (ABq, 2H), 4.70 (ABq, 2H), 4.20-4.05 (m, 4H ), 2.77 (s, 3H); 13C NMR (75 MHz, CDC13) δ 177.3, 167.6, 154.9, 152.7, 150.1, 144.5, 143.3, 138.1, 136.2, 132.5, 131.6, 129.0, 123.7, 123.1, 122.9, 122.2, 112.4, 109.6, 99.0, 79.7, 64.6, 64.1, 57.7, 43.3, 26.5; MS (ES+) 143924-sp-20091127-5 -838 - 201020257 m/z 443.9 (Μ + 1) 〇Example 12.64 Ν-(2- Aminoethyl)-2-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxan) Alkenyl -8,3% Shu indol] -Γ (2Ή) -?-Yl) methyl] piperidine hydrochloride or Bauer 2carboxamide two _3_

In a 50 ml round bottom flask, packed with 2_[(2, keto-2,3_dihydrospiro [bito-and-[2,3-g][l,4] benzodioxane) ]_ι,(2Ή)-基)曱基风咬_3-Rebel acid (0.43g '1.0mmoler), 2-aminoethylaminocarbamic acid third_butyric vinegar (〇J2 克' 2.0耄莫Ear), 1-ethyl-3-(3-didecylaminopropyl)carbodiimide hydrochloride (0.26 g ' 1.35 house Moule), 1-Phenylbenzotriwa (〇·2 〇克, 1.5 mmol, Ν-mercapto porphyrin (〇. 4 ml, 3.6 mmol) and hydrazine, Ν-dimercaptocaramine (7 ml). The reaction mixture was stirred with EtOAc (EtOAc m. Add 4 Μ solution of hydrochloric acid in dioxanol and mix the reaction mixture for 16 hours, dilute with sew (5 〇 ml), and filter to obtain Ν-(2-aminoethyl)-2-[ (2'--yl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-1·( 2Ή)-yl)methyl] octazone-3-carboxylamidine dihydrochloride (0.31 g '57%) as an off-white solid: iHNMR (300 MHz, CDC13) δ 10.01 (s, 2H), 9.02 (t , J = 5.4 Hz, 1H), 8.45 (dd, J = 4.8, 1.5 Hz, 1H), 8.20 (s, 2H), 8.10 (dd, J = 7.8, 1.5 Hz, 1H), 7.41 (dd, J = 7.8, 4.9 Hz, 143924-sp-20091127-5 •839· 201020257 1H), 7.20-7.08 (m, 2H), 6.99-6.86 (m, 2H), 6.46 (s, 1H), 6.43 (s, 1H) , 5.26 (ABq, 2H), 4.71 (ABq, 2H), 4.19-4.05 (m, 4H), 3.58-3.47 (m, 2H), 3.06-2.93 (m, 2H) ; 13 C NMR (75 MHz, CDC13 &lt;5 177.4,167.6,154.9,152.9, 150.0, 144.5, 143.3, 138.1, 137.1, 132.5, 130.9, 129.0, 123.8, 123.1, 122.9, 122.2, 112.3, 109.7, 99.0, 79.7, 64.6, 64.1, 57.7, 43.2, 38.8, 37.6; MS (ES+) m/z 472.9 (M + 1). Example 12.65 N-(2-Fluorophenyl)-4-[(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxime Synthesis of terpene-8,啕哚]-1·(2Ή)-yl)mercapto]benzamide

4-[(2'-keto-2,3-dihydrospiro[吱D南和[2,3-g][l,4]benzodioxanthene-8,3'-♦ ]-1'(2Ή)-yl)mercapto]benzoic acid (0.400 g, 〇·93 mmol) in a stirred solution in anhydrous gas (20 ml), adding dimethyl sulfoxide (〇) 27 ml ' 3.7 mmol) ^ The solution was heated under reflux for 2 hours and concentrated in vacuo to give the gasified 4-[(2,-keto-2,3-dihydrospiro[[ 2,3-g][l,4]benzodioxanthene-8,3'-峋哚]-ν(2Ή)-yl)methyl]phenylhydrazine (0.45 g), as a pale yellow solid . In a solution of 2-fluoroaniline (0.1 ml, 1 mmol) with triethylamine (〇43 mL, 3.1 mmol) in anhydrous dichloromethane (1 mL) Next, add gasification 4_((2·_keto_3,7-dihydro-2-indole [benzofuro[5'6 b][l,4]-oxy-terpinene_8,3'_ Indoline]-indole, yl)methyl)benzoquinone (1) gram, 1. 〇 millimol P The reaction mixture was stirred at ambient temperature for 42 hours, 143924-sp-20091127-5 • 840-201020257 and Wash with 10% w/v hydrochloric acid (10 ml), water (1 mL) and brine (1 mL). The organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with hexane / ethyl acetate (1/1) to give N-(2-fluorophenyl)-4-[(2,-keto-2,3) -Dihydrospiro[吱,[2,3-g][1,4]benzodioxanthene_8,3·-吲哚]-1·(2Ή)-yl)indenyl]benzoquinone Indoleamine (0.262 g '49%) as colorless solid: mp 245-251. (: ; iH NMR (300 MHz, CDC13) δ 8.48-8.43 (m, 1H), 8.11-8.04 (m, 1H), 7.88 (d, J = 8.1 Hz, 2H), 7.46 (d, J = 8.1 Hz , 2H), 7.24-7.02 (m, 6H), 6.75 (d, J = 7.8 Hz, 1H), 6.52 (s, ® 1H), 6.24 (s, 1H), 5.16 (d, J = 15.9 Hz, 1H ), 4.95 (d, J = 8.7 Hz, 1H), 4.89 (d, J = 15.9 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.21-4.10 (m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 177.6, 164.9, 155.3, 152.7 (d, J = 241.4 Hz), 144.7, 141.7, 140.0, 138.3, 134.1, 132.2, 128.8, 127.8 (d, J = 4.1 Hz), 126.4 (d , J = 9.8 Hz), 124.7-124.6 (m), 124.1, 123.7, 121.8, 120.8, 114.8 (d, J = 19.1 Hz), 111.4, 109.1, 99.5, 80.1, 64.5, 63.9, 58.0, 43.8; MS ( ES+) m/z 523.0 (M + 1). Example 13 ®5-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] Synthesis of furan-3,3·-吲哚]-Γ(2Ή)- 'base) fluorenyl]pyran-2-hypoacid

5·[(Ζ-keto-5,6-dihydrospiro[benzo[1,2-b : 5,4-b·]difuran-3,3·-啕哚]-Γ(2Ή) Methyl-methyl]furan-2-carboxylate (5.5 g, 13.0 mmol) with sodium hydroxide (1.04 g, 26.0 mmol) in water (100 mL) with methanol (4 mL) The solution in 143924-SP-20091127-5 -841 - 201020257 was spoiled at 65 ° C for 16 hours. The solvent methanol was evaporated under reduced pressure and the residue was cooled in an ice-b] and acidified to pH L2 with 10% hydrochloric acid. The solid matter was filtered off and recrystallized from ethanol (100 ml) to give 5_[(2,-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4 7' 2 咬 _ 3,3,-吲哚]-ΐ'(2Ή)-yl)methyl]furan-2-carboxylic acid (5.10 g, 92%) as a colorless solid: 1 η NMR (300 ΜΗζ, CDC13) δ 7.36-6.92 (m, 5Η), 6.51 (s, 1H), 6.44 (d, J = 3.5 Hz, 1H), 6.40 (s, 1H), 5.02 (ABq, 2H), 4.81 (ABq, 2H ), 4.51 (t, J = 8.6 Hz, 2H), 3.04-2.91 (m, 2H); 13C NMR (75 MHz, CDC13) δ 177.2, 161.6, 160.9, 159.6, 153.7, 145.0, 142.1, 132.7, 129.1, 124.0, 123.7, 121.0, 120.4, 119.6, 119.1, 111.1, ® 109.7, 92.9, 80_0, 72.6, 57.4, 37.3, 28.8; MS (ES+) m/z 403.8 (M + 1). Example 13.1 N,N-Dimercapto-5-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4,7]]difuran-3,3, -吲嗓]-Γ(2Ή)-yl)methyl]mum-2-_2carboxamide synthesis

5-[(2'-keto-5,6-dihydrospiro[benzo-like 7:5,4-7,]difuran-3,3-吲哚]-Γ(2Ή)-yl)methyl吱 -2--2-carboxylic acid (4.85 g, 12 mmol), two gasified sulfoxide (11.90 g '100 mmol) and a few drops of ν, Ν-dimethyl decylamine in gas imitation ( The mixture in 60 ml) was stirred at ambient temperature for 16 hours. The solvent and excess sulfite dichloride were evaporated under reduced pressure. The residue was dissolved in di-methane (5 Torr). In the above solution (5 ml, ι·2 mmol), add dimethylamine hydrochloride (0.81 g '10 mmol) and triethylamine (1. 1 g, 10 mmol) ^ The mixture was mixed for 3 hours at ambient temperature. The reaction mixture was diluted with EtOAc - EtOAc - EtOAc (EtOAc) (EtOAc) (EtOAc) The filtrate was evaporated under reduced pressure, and the residue was purified mjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj Benzyl-5,6-dihydrospiro[benzo[ub:5,4-7,]difuran-3,3,-啕哚]-Γ(2Ή)-yl) fluorenyl]pyran-2-carboxyindole Amine (0.22 g, 42%) as a colorless solid: iHNMR (300 MHz, CDC13) δ 7.31-6.90 (m, 5H), 6.43-6.37 (m, 3H), 4.97 (ABq, 2H), 4.78 (ABq, 2H), 4.52 (t, J = 8.6 Hz, 2H), 3.11 (s, 6H), 2.96 (t, J = 8.6 Hz, 2H); 13C NMR (75 MHz, CDC13) (5 177.2, 161.6, 161.0, 159.4, 151.3, 147.5, ® 142.2, 132.6, 129.1, 124.1, 123.7, 121.0, 120.4, 119.5, 116.8, 110.4, 109.8, 92.9, 80.1, 72.6, 57.4, 37.1, 28.8; MS (ES+) m/z 431.1 ( M + 1). Example 13.2 N-Mercapto-5-[(2,-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3 ,3,- 哚 哚]-Γ(2Ή)-yl)methyl]pyran-2-carboxylamine synthesis

N-CH3 Η

Following the procedure as described in Example 13.1, and carrying out irrelevant changes, the dimethylamine hydrochloride was replaced with methylamine hydrochloride to give the oxime-methyl-5-[(2^ fluorenyl-5,6- Dihydrospiro[p- and [l,2-b:5,4-b']difuran-3,3'-indole]-indole (2Ή)-yl)methyl]furan-2-carboxamide 37%), as a colorless solid: 4 NMR (300 MHz, CDC13) δ 7.29-6.89 (m, 5H), 6.66 (s, 1H), 6.42-6.35 (m, 3H), 4.91 (ABq, 2H), 4.78 (ABq, 2H), 4.53 (t, J = 8.5 Hz, 2H) 2.98-2.87 (m, 5H) ; 13 C NMR (75 MHz, CDCI3) δ 177.8, 161.9, 161.3, 158.7, 150.5, 148.0, 141.3, 132.5, 128.9, 124.1, 123.9, 120.0, 119.9, 118.8, 114.8, 111.1, 108.8, 93.3, 80.4, 72.4, 57.7, 143924-sp-20091127-5 - 843 - 201020257 37.2,29·0,25.8 ; MS (ES+ ) m/z 417.2 (Μ + 1). Example 13.3 2-[(2-keto-5,6-dihydrospiro[benzo[1,2-7:5,4?|]2 sniffer-3,3,-compliance]-1, (2 Synthesis of 11)-yl)methyl]-1,3-oxazol-4-carboxyguanamine

Following the procedure as described in Example 13.1, and performing an insignificant change, the dimethylamine hydrochloride was replaced with a 4 Μ ammonia solution in dioxane, using 2_[(2, keto-5,6-di Hydrogen snail [benzo[l,2-b:5,47']dipyran-3,3,-吲嗓]-1,(2Ή)-yl) fluorenyl]-1,3′′ azole- 4-carboxylic acid substitution 5-[(2,-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3-W哚]- 1'(2Ή)-yl)methyl]mol-2-carboxylic acid to give 2-[(2,-keto-5,6-di-argon][benzo[l,2-b: 5,4 -1&gt;'] Diterpene-3,3,-吲嗓]-Γ(2Ή)-yl)methyl]-1,3-Noconazole-4-carboxamide (19%) as a colorless solid :1 η NMR (300 MHz, CDC13) δ NMR (300 MHz, CDC13) δ 8.55 (s, 1H), 7.53 (d, J = 10.2

Hz, 2H), 7.33-6.99 (m, 4H), 6.54 (s, 1H), 6.38 (s, 1H), 5.22-5.01 (m, 2H), 4.75 (ABq, 2H), 4.46 (t, J = 8.8 Hz, 2H), 2.92 (t, J = 8.6 Hz, 2H); 1 3 C NMR (75 MHz, CDCI3) δ ΠΊ3, 161.9, 161.6, 160.9, 159.2, 143.2, 142.2, 136.8, 132.5, 129.2, 124.1 , 123.8, 120.8, 120.4, 119.7, 109.6, 92.8, 80.0, 72.5, 57.3, 37.4, 28.7; MS (ES+) m/z 403.8 (M + 1) 〇 Example 13.4 N,N-Dimethyl-2-[ C-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b.]difuran-3,3·-p]-indole (2Ή)-yl)methyl Synthesis of]-l,3-&lt;»Sal-4-Rebel amine 143924-sp-20091127-5 -844- 201020257

H3c-n CHo according to the procedure as described in Example 13.1, and with irrelevant changes, use 2-[(2,-keto-5,6-dihydrospiro[benzo[u_b: 5,4-7, Difuran_3,3,thraquinone]-1'(2Ή)-yl)methyl]-1,3-carbazole-4-carboxylic acid substitution 5-[(2,-keto-5,6- Dihydrospiro

[Benzo[l,2-b:5,4-b']difuryl _3,3_w 哚]_r(2,H)-yl)methyl] oleno-2-carboxylic acid, N,N-di Methyl-2-[(2,-keto-5,6-dihydrospiro[benzo[1,2:7,5,7]]------3,3'----] 2Ή)-yl) fluorenyl]_ι, 3_ oxazolidine _4_carboxamide (3 〇%), as a colorless solid: 4 NMR (300 MHz, CDC13) &lt;5 8.09 (s, 1 Η), 7.27- 6.86 (m, 4H), 6.50 (s, 1H), 6.40 (s, 1H), 5.08 (ABq, 2H), 4.82 (ABq, 2H), 4.52 (t, J = 8.6 Hz, 2H), 3.29 (s , 3H), 3.06 (s, 3H), 2.97 (t, J = 8.6 Hz, 2H); MS (ES+) m/z 431.8 (M + 1). Example 13.5 ❹ N-cyclopropyl-2_[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxan-7,3,_ΡΡ丨嗓] Synthesis of -1'(2Ή)-yl) sulfhydryl]-1,3-nazao-4-treazone

2-((2'-keto-6H-spiro[benzofuro[6,5-d][l,3]dioxanthene·7,3,·dihydroindole]-Γ- Base) carbazole-4-carboxylic acid (0.41 g, 1.0 mmol), benzyl benzotriazole (0.20 g, 1.5 mmol) and 1-ethyl-3-(3-di) Methylaminopropyl) Cleaved diimine hydrochloride (0.29 g, 1.5 mmol) in a solution of dichloromethane (10 143 924-sp-20091127-5-845-201020257 liters) Minutes followed by the addition of cyclopropylamine (0.8 mL). The solution was stirred at ambient temperature for 16 hours. Dilute with dichloromethane (100 mL), washed with distilled water (2.times.50 mL), dried over magnesium sulfate, dried, and concentrated to dryness in vacuo. Purification by flash chromatography using ethyl acetate in hexane (gradient: 50% to 75%) to give N-(l-mercaptoethyl)-2-[(2.喃[2,3-f][l,3]benzodioxanthene_7,3,_w p]-1'(2Ή)-yl)methyl]-1,3-11 -4-Rebelamine (0.40 g, 91%), as a colorless solid: mp 188-191 ° C; 4 NMR (300 MHz, CDC13) 5 8.14 (s, 1 Η), 7.28-7.22 (m, 1H), 7.19 (d, J = 6.8 Hz, 1H), 7.07 (dd, J = 7.4, 7.4 Hz, 1H), 6.85 (d, J = 7.7 Hz, 2H), 6.49 (s, 1H), 6.16 (s, 1H) ), 5.85 (ABq, 2H), 5.04 (ABq, 2H), 4.81 (ABq, 2H), 2.82 (m, 1H), 0.85-0.77 (m, 2H), 0.64-0.58 (m, 2H) ; 13C NMR (75 MHz, CDC13) 5 177.2, 161.3, 158.1, 155.8, 149.0, 142.4, 141.8, 141.0, 136.6, 132.0, 129.1, 124.15, 124.10, 119.2, 108.6, 103.0, 101.6, 93.7, 80.2, 58.2, 37.1, 22.3 , 6.60, 6.55; MS (ES+) m/z 446.2 (M + 1). Example 13.6 N-(l-methylethyl)-2-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxol-7,3Wb Synthesis of ~1'(2Ή>gt)-based γ-based H,3_, oxazolidine carboxamide

According to the procedure as described in Example 13.5, and irrelevant changes were made, the cyclopropylamine was replaced with isopropylamine to obtain N_(1methylethyl) 2 [(21 oxo[吱 并[2,3- f][l,3]benzodioxolene _7 3,吲哚]r(2,H)yl)methyl]13_ 3 ° sit-4-reamine (17%) as a colorless solid : melting point 182 183〇c ; ! η NMR (3〇〇143924-SP-20091127-5 -846- 201020257 MHz, CDC13) δ 8.12 (s, 1H), 7.31-7.17 (m, 2H), 7.08 (dd, J = 7.5, 7.5 Hz, 1H), 6.88 (s, J = 7.8 Hz, 1H), 6.61 (d, J = 7.5 Hz, 1H), 6.50 (s, 1H), 6.17 (s, 1H), 5.85 ( d, J = 4.6 Hz, 2H), 5.05 (ABq, 2H), 4.82 (ABq, 2H), 4.20 (m, 1H), 1.22 (d, J = 6.5 Hz, 6H) ; 13C NMR (75 MHz, CDC13 ) δ 1112, 159.1, 158.0, 155.8, 149.1, 142.4, 141.8, 141.0, 136.9, 132.0, 129.1, 124.2, 119.2, 108.7, 103.0, 101.6, 93.7, 80.2, 58.2, 41.2, 37.1, 29.7, 22.7; MS ( ES+) m/z 448.2 (M + 1). Example 13.7 N-(2-Fluorophenyl)-2-(2'-keto-2,3-dihydrospiro[2,3-g][l,4]benzodioxanthene Synthesis of -8,3'-吲哚]-Γ(2Ή)-yl)acetamide

丨V

(2'-keto-2,3-dihydrospiro[furo[2,3_g][i,4]benzodioxanthene φ 吲嗓Η'(2·Η)-yl)acetic acid ( 0.53 g ' 1.50 mmol, 2-fluoroaniline (0.2 mL, 2.1 mmol) and triethylamine (0.5 mL, 35 mmol) in chloroform (3 mL), add 2- Ethoxy small ethoxycarbonylhydroporphyrin (0.48 g, 1.94 mmol). The reaction mixture was heated under reflux for 1 hour, allowed to cool to ambient temperature, diluted with ethyl acetate, and successively water, 1% w/v hydrochloric acid, water, 1% w/v aqueous sodium hydroxide, water Wash with salt water. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate/hexane (1/3) 143924-sp-20091127-5-847-201020257 to obtain the group (2-fluorophenyl)-2- (2'-keto-2,3-dihydrospiro[furo[2,34][1,4] benzodioxanthene-8, 吲哚]-Γ(2Ή)·yl) acetamidine Amine (0.08 g, 12%): mp 117-119 ° C (ethyl acetate / hexane); iH NMR (300 MHz, CDC13) 5 8.24-8.22 (m, 1H), 8.05-7.90 (m, 1H) , 7.33-6.95 (m, 6H), 6.50-6.47 (m, 1H), 6.33-6.30 (m, 1H), 4.94-4.89 (m, 1H), 4.68-4.49 (m, 4H), 4.17-4.09 ( m, 4H); 13C NMR (75 MHz, CDC13) δ 178.2, 164.6, 155.2, 144.7, 141.3, 138.4, 131.9, 129.1, 125.6, 124.9, 121.8, 120.4, 115.0, 114.8, 111.7, 108.9, 99.4, 80.0, 64·6, 63.8, 58.0, 45.1; MS (ES+) m/z 446.8 (M+l). Example 13.8 2-[(3-Methyl-2'-oxaspiro[furo[3,2-f][l,2] benzisoxazole-5,3·-嘀哚]-Γ(2Ή) Synthesis of -yl)methyl]-l,3-oxazole-4-carboxylic acid

According to the procedure as described in Example 13, and the insignificant change was carried out, 2-[(3-methyl-2-oxospiro[[,2-f][l,2] benzo] was used. Oxazole-5,3,-嘀哚]-Γ(2Ή)-yl)methyl]-1,3-oxazole-4-carboxylic acid methyl ester substituted 5-[(2,-keto-5,6 - Dihydrospiro[benzo[l,2-b: 5,4-difuran-3,3'-indole, (2Ή)-yl)methyl]pyran-2-carboxylic acid vinegar 2-[(3-Mercapto-2'-oxaspiro[吱,[3,2-f][i,2] benzisoxazole-5,3,-4哚]-1·(2Ή) )-yl)methyl]-1,3-oxazole-4-carboxylic acid (69%) as a colorless solid: 1 NMR (300 MHz, DMSO-d6) &lt;5 13.13 (s, 1H), 8.70 ( s, 1H), 7.74-7.71 (m, 1H), 7.40-7.34 (m, 1H), 7.26-7.23 (m, 2H), 7.07-7.02 (m, 2H), 5.28-5.22 (m, 2H), 5.00-4.90 (m, 2H), 2.39 (s, 3H); MS (ES+) m/z 417.8 (M + 1). 143924-sp-20091127-5 -848- 201020257 Example 13.9

,N-Dimethyl-2-[(3-methyl-2'-oxaspiro[p-benzo-benzo-p-pyrazole-5,3 smu]-1 (2 H)-yl)methyl] Synthesis of 4'3's saliva_4_ apoein 2-[(3-methyl-2'-oxaspiro[吱,[3,2-f][i,2] benzisoxazole _5,3,_吲© p-H'(2'H)-yl) fluorenyl]-1,3 』 吐-4- oxic acid (0.32 g, 〇 · 76 mmol), diamine Hydrochloride (0.13 g '1.52 mmol), μhydroxybenzotriazole hydrate (0.16 g, 1.17 mmol), 1-ethyl-3-(3-dioxylpropyl)-carbonization Diimine hydrochloride (0.21 g, 1.07 mmol), 4-methylmorpholine (0.23 ml, 2.07 mmol) and anhydrous hydrazine, hydrazine-dimethylformamide (1 mL) The mixture was dropped for 16 hours at ambient temperature. The reaction mixture was concentrated in vacuo and the residue was crystallised from diethyl ether to afford sd, s-dimethyl-2-[(3- syl- 2 - oxab f][l,2]benzisoxazole-5,3'-accurate]-Γ(2Ή)-yl)indenyl]-1,3-oxazole 4-sulfanylamine (0.23 g, 68% , as a colorless solid: mp 87-89 ° C (diethyl ether); iHNMR (300 MHz, CDC13) (5 8.10 (s, 1H), 7.48-7.5 (m, 1H), 7.31-7.25 (m, 1H), 7.14-7.11 (m, 1H), 7.05-6.95 (m, 3H), 5.28-5.06 (m, 3H), 4.87-4.84 (m, 1H), 3.32 (s, 3H), 3.06 (s, 3H), 2.43 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 175.8, 164.0, 161.7, 158.2, 157.1, 154.9, 143.7, 141.3, 137.2, 130.1, 129.5, 124.0, 123.9, 123.2, 118.0, 109.3, 108.6, 107.9, 81.3, 56.3, 38.4, 37.5, 36.2, 9.8; MS (ES+) m/z 444.8 (M+l) 〇 Example 13.10 143924-sp-20091127-5 -849- 201020257 1'-(3-Aminopropyl -5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3,3,-啕哚]-2' (1Ή&gt; ketone synthesis

2-[3-(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3,-吲嗓]-1 Add a single sheet of '(2Ή)-yl)propyl]-1H-isoindole_1,3 (2,2-dione (1.25 g, 2.70 mmol) in ethanol (25 mL) Hydrate (〇7〇 ml, 8.2 mmol). The reaction mixture was stirred at ambient temperature for 3 days. During this time, the precipitate was deposited. The solid was collected by filtration and purified by column chromatography with acetic acid. Ethyl acetate/sterol/7-sterol ammonia (1〇/1/〇2) is dissolved, and Γ-(3-aminopropyl)-5,6-dihydrospiro is obtained. [Benzene is like 7:5. 4,7,]difuran_3 3,·(5) 嗓]-2'(1Ή)-ketone' is a yellow oil: Ms (ES+) ^ 336 9 (M + υ. Example 13.11 Ν-[3-(2'- Keto-5,6-dihydrospiro[benzo:5,4?-]difuran-3,3,-accord]-1'(2Ή)-yl)propyl]_2-(trifluoromethoxy Synthesis of benzamidine

Γ-(3-Aminopropyl)-5,6-dihydrospiro[benzo[u7:5 4_bi]difuran_3 3,β哚]-2,(1Ή), (0.20 g, 〇 .59 mmol) in a solution of anhydrous di-methane (9 ml), triethylamine (〇1 mL, 〇71 mmol), followed by gasification of 2-(trifluoromethoxy)benzene Hey. The reaction mixture was stirred at ambient temperature for 20 hours and allowed to shrink in vacuo. Purification of the residue by column chromatography, 143924-sp-20091127-5 -850· 201020257 and obtained Ν-[3-(2·-keto-5,6-dihydrospiro[benzo[i,2- b: 5,4-b,]difuran-3,3,-equivalent]-indole (2Ή)-yl)propyl]-2-(trifluoromethoxy)phenylamine (0.21 g, 67 %), as a colorless foam: melting point 65-7 (TC; 1H NMR (300 MHz, CDC13) (5 7.81 (dd, J = 7.6, 1.7 Hz, 1H), 7.47 (ddd, J = 9.4, 7.6, 1.5 Hz, 1H), 7.39-7.30 (m, 3H), 7.20 (d, J = 6.9 Hz, 1H), 7.09 (dd, J = 7.5, 7.5 Hz, 1H), 6.95 (d, J = 7.9 Hz, 1H ), 6.47 (s, 1H), 6.41 (s, 1H), 4.90 (d, J = 9.0 Hz, 1H), 4.67 (d, J = 9.0 Hz, 1H), 4.53 (t, J = 8.6 Hz, 1H ), 4.02-3.83 (m, 2H), 3.58-3.33 (m, 2H), 2.99 (t, J = 8.6 Hz, 2H), 2.05-2.01 (m, 2H) ; 13C NMR (75 MHz, CDC13) δ ® 179·0, 164·9, 161.9, 161.3, 145.7, 141.8, 132.8, 131.8, 130.7, 129.3, 128,9, 127.3, 124.1, 123.7, 121.5, 120.3 (d, JC.F= 259.2 Hz), 120.0 , 119.8, 118.7, 108.4, 93.3, 80.5, 72.4, 57.8, 37.1, 36.1, 29.0, 27.0; MS (ES+) m/z 524.5 (M + 1). Example 14 r-[(2S)-2-hydroxypropane Base]-5,6-dihydrospiro[benzo[i,2-b: 5,4,7,]difuran _3,3W| 哚]-2'(1Ή)-net synthesis

1 -{(2S)-2-[(benzyloxy)decyloxy]propyl b 5,6-dihydrospiro [stupid [丨27: 5,4-btfuran-3,3'-啕哚]-2'(1,H)-one (2.4 g, 5.2 mmol), palladium/carbon Φ.24 g, 1% by weight) & 3M hydrochloric acid (5 ml) in absolute ethanol (5 〇) The mixture was stirred in cc) and hydrogenated at 50 psi for 6 hours using a Parr hydrogenation apparatus. The mixture was filtered through celite and concentrated to dryness in vacuo. The residue was purified by flash chromatography using ethyl acetate (25% 143924-sp-20091127-5 • 851· 201020257 to 50% gradient) to give l'-[(2S)-2 -hydroxypropyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3·-吲哚]-2\1Ή)-one (1.37 Gram, 78%), as colorless solid: mp 171-174. (: ; 1H NMR (300 MHz, DMSO-d6) ά 7.28 (dd, J = 7.7, 7.7 Hz, 1H), 7.16 (d, J = 7.4 Hz, 1H), 7.04 (dd, J = 7.5, 7.5 Hz , 1H), 6.97 (dd, J = 7.8, 3.5 Hz, 1H), 6.49 (d, J = 10.2 Hz, 1H), 6.39 (d, J = 1.4 Hz, 1H), 4.91 (dd, J = 9.0, 0.5 Hz, 1H), 4.66 (dd, J = 9.0, 0.6 Hz, 1H), 4.51 (dt, J =: 8.6, 1.0 Hz, 1H), 4.29-4.11 (m, 1H), 3.90-3.66 (m, 2H), 3.07-2.87 (m, 2H), 2.41 (dd, J = 32.9, 5.5 Hz, 1H), 1.28 (dd, J = 6.3, 1.1 Hz, 3H) ; 13C NMR (75 MHz, DMSO-d6) &lt;5 179.2, 161.8 (2), 161.3 (2), 142.6 (2), 132.9 (2), 128.7 (2), 123.9 (2), 123.5, 120.2 (2), 120.0 (2), 118.8 (2 ), 108.9 (2), 93.2 (2), 80.6 (2), 72.4 (2), 66.5 (2), 57.8 (2), 48.1 (2), 29.0 (2), 21.4; MS (ES+) m/ z 338.0 (M + 1). Example 14.1 l'-[(2S)-2-(Benzyloxy)propyl]-5,6-dihydrospiro[benzo[i,2-b: 5,4- b,]二吱.South-3,3, 哚]]-2'(1'11)-ketone synthesis

In l'-[(2S)-2-hydroxypropyl]-5,6-dihydrospiro[benzo[1,2-7:5,4-7,]difuran-3,3,·呻哚]- 2·(1Ή)-ketone (0.19 mg, 0.56 mmol) in a stirred solution in anhydrous tetrahydrofuran (1 mL), sodium hydride (6% dispersion in mineral oil, 0.03 g, 0.71) Millions) The solution was stirred at ambient temperature for a few minutes and then cesium bromide (0.14 g, 0.84 mmol) was added. The reaction mixture was stirred for 16 hours. The solution was allowed to cool to ambient temperature, filtered, and concentrated to dryness in vacuo 143924-sp-20091127-5 -852- 201020257. The residue was purified by flash chromatography using ethyl acetate (25%) eluted elute Snail [benzo[l,2-b·· 5,4-b']difuran-3,3,-吲哚]ΚΙΉ)-one (0.20 g, 77%) as colorless solid: m.p. °C; 1H NMR (300 MHz, CDC13) (diastereomer) δ 7.30-6.97 (m, 9H), 6.38 (s, 1H), 6.33 (d, J = 36.0 Hz, 1H), 4.84 ( Dd, J = 21.7, 8.9 Hz, 1H), 4.68-4.55 (m, 2H), 4.49 (dt, J = 8.6, 0.8 Hz, 2H), 4.40 (dd, J = 12.0, 3.8 Hz, 1H), 4.01 -3.83 (m, 2H), 3.80-3.68 (m, 1H), 2.88 (t, J = 8.6 Hz, 3H); 13 C NMR (75 MHz, CDC13) (diastereomer) 6 178.1 (2 ), ® 161.7 (2), 161.3 (2), 143.0 (2), 138.3 (2), 132.7, 128.6, 128.3 (2), 127.5 (2), 127.3, 123.6 (2), 123.2, 120.3 (2), 119.8 (2), 118.9 (2), 109.7 (2), 93.2, 80.7 (2), 73.2, 72.8, 72.4, 70.9, 70.7, 57.6, 46.1 (2), 29.0 (2), 17.7 (2); MS ( ES+) m/z 428.0 (M +23). Example 14.2 l'-{(2S)-2-[(4-Fluorobenzyl)oxy; Ipropyl}_5,6-dihydrospiro[benzopyrene: 5,4_b.] difuran-3, Synthesis of 3'-threshold]-2,(1Ή)-ketone

According to the procedure as described in Example 14.1, and irrelevant changes were made, the benzyl bromide was replaced with desertified 4-fluorobenzyl to obtain r_{(2S)_2_[(4-fluorobenzyl)oxy]propyl} -5,6-dihydrospiro[benzo[1,2-7:5,4-b']difuran-3,3'-峋哚]-2'(1Ή)-one (70%) ' is colorless Solid: melting point 55_6〇〇c ; ! 丽 丽 &amp; (3〇〇CDCl3) δ 7.30-7.20 (m, 1H), 7.17-6.97 (m, 5H), 6.93-6.84 (m, 2H), 6.38 (s , 1H), 6.30 (d, J = 36.9 Hz, 1H), 4.84 (dd, J = 13.8, 8.9 Hz, 1H), 4.65-4.53 (m, 2H), 143924-sp-20091127-5 -853« 201020257 4.49 (dt, J = 8.6, 1.2 Hz, 2H), 4.36 (dd, J = 11.8, 5.4 Hz, 1H), 4.00-3.83 (m, 2H), 3.79-3.66 (m, 1H), 2.96-2.80 ( m, 2H), 1.29 (d, J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDC13) δ 178.1, 162.2, 161.3, 143.0, 134.0, 132.7, 129.0, 128.5, 123.7, 123.2, 120.2, 119.8, 118.8, 115.2, 114.9, 93.2, 80.6, 73.3, 72.9, 72.4, 70.0, 57.6, 46.0, 29.0, 17.6; MS (ES+) m/z 445.8 (M + 1) ° Example 14.3 14(2S)-2-( Acridine-2-ylmethoxy)propyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3'-indole]one Combination to make

Following i. _[(2s)-2-( Acridine-2-ylmethoxy)propyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-吲哚]- 2'(1Ή)-ketone (69%) ' is a colorless solid: mp 46-54 ° C; 1H NMR (300 MHz, CDC13) δ 8.49-8.41 (m, 1 Η), 7.50 (m, 1H), 7.35- 6.87 (m, 6H), 6.54-6.13 (m, 2H), 4.94-4.80 (m, 1H), 4.80-4.67 (m, 1H), 4.66-4.32 (m, 4H), 4.10-3.63 (m, 3H) ), 2.97-2.57 (m, 2H), 1.62-0.76 (m, 3H); 13C NMR (75 MHz, CDCI3) δ 178.1, 161.7, 158.5, 148.8, 143.0, 136.6, 132.7, 128.6, 123.7, 123.2, 122.2 , 121.0, 120.3, 119.8, 118.8, 109.4, 93.1, 80.5, 73.5, 72.3, 71.7, 57.6, 45.9, 28.9, 17.5; MS (ES+) m/z 428.74 (M + 1). Example 14.4 Γ-(3- Butyl)-5,6-dihydrospiro[benzo[1,2:7,5,4-b,]difuran-3,3,-θ| 143924-sp-20091127-5 854· 201020257

3-(2,-keto-5,6-dihydrospiro[benzo[i,2-b:5,47']difuran_3,3,_巧普朵]_ 1'(2Ή Add methylmagnesium bromide (0 35 ml, 3 Μ φ diethyl ether solution '1.05) at 0 ° C in a stirred solution of propionaldehyde (0.34 g '1.00 mmol) in tetrahydrofuran (9 ml) Millions of ears). The reaction mixture was stirred for 3 hours under TC. The reaction was quenched with EtOAc EtOAc (EtOAc)EtOAc. Concentrate the filtrate in vacuo. [The residue was subjected to column chromatography using ethyl acetate (20% to 40% gradient) in hexane to give 1-(3-hydroxybutyl)-5,6-dihydrogen. Snail [benzo[l,2-b:5,4-b']difuran-3,3,-呻哚]-2,(1Ή)-one (0.21 g, 59%): m.p. 64-66 C (diethyl ether / hexane); 1H NMR (300 MHz, CDC13) 5 7.33-7.28 (m, 1H), 7.19-7.15 (m, 1H), 7.09-7.03 (m, 1H), 6.94 (d, J = 6.0 Hz, 1H), © 6.46-6.40 (m, 2H), 4.92~4.87 (m, 1H), 4.69-4.62 (m, 1H), 4.564.49 (m, 2H), 4.21-4.09 (m, 1H) ), 3.76-3.62 (m, 2H), 3.22 (br s, 1H), 3.03-2.95 (m, 2H), 1.88-1.63 (m, 2H), 1.24-1.19 (m, 3H) ; MS (ES+) m/z 352.1 (M + 1). Example 14.5 1'-(4,4,4-Trifluoro-3-hydroxybutyl)-5,6-dihydrospiro[benzo[1,2:7:5, 4-7|] Synthesis of difuran_3,3,?h]-2'(1Ή)-ketone 143924-sp-20091127-5 - 855 - 201020257

3-(2-keto-5,6-one wind snail [stupid [l,2-b: 5,4-b'] dioxin-3,3'-p 嗓]_ 1'( 2Ή)-yl)propanal (0.34 g, 1.00 mmol) in tetrahydrofuran (1 mL) in a stirred solution, at -78 Τ:, add fluorinated planer (〇.8 gram, 5.26 mmol) Ear) with difluorodecyl fluorene-based stone court (0.25 ml ' 1.69 mM). The reaction mixture was stirred for 18 hours while allowing the temperature to slowly warm to ambient temperature. The reaction was quenched with methanol, stirred at ambient temperature for one hour and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography using ethyl acetate (20% to 40% gradient) in hexane to give 1-(4,4,4-tris-3-hydroxybutyl)-5. ,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-吲哚]-2Χ1Ή)-one (0.24 g '58%): melting point 124- 126 ° C (diethyl ether / hexane); 1H NMR (300 MHz, CDC13) δ 7.36-7.31 (m, 1H), 7.22-7.19 (m, 1H), 7.13-7.08 (m, 1H), 6.94 (d, J = 9.0 Hz, 1H), 6.45-6.41 (m, 2H), 4.89-4.70 (m, 1H), 4.67-4.63 (m, β 1H)} 4.56-4.49 (m, 2H), 4.24-4.10 (m , 1H), 4.01-3.73 (m, 3H), 3.02-2.95 (m, 2H), 2.11-2.05 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 179.5, 162.1, 162.0, 161.4, 161.3 , 141.5, 132.7, 129.1, 124.3, 124.0, 120.2, 119.6, 118.8, 118.5, 108.4, 93.4, 80.3, 72.4, 67.8, 57.9, 36.2, 28.9; MS (ES+) m/z 405.7 (M + 1). Example 15 3-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3%5bd]-1' ( Synthesis of 2Ή)-yl)propanal 143924-sp-20091127-5 -856- 201020257

Γ-(3-propyl)-5,6-dihydrospiro[benzo-like seven:5,4-seven-furan-furan-3,3,_pb丨哚]-2'(1Ή)-鲷(2.00 Gram, 5.92 mmol) Add Dess-Martin over-magnetic (3.70 g, 8.46 mmol) in a solution of di-methane (1 mL). The reaction mixture was stirred at 0 C for 17 hours, diluted with ethyl acetate and washed with a 1% aqueous sodium thiosulfate solution and saturated sodium hydrogen carbonate solution and brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo, and the residue was applied to EtOAc EtOAc EtOAc EtOAc EtOAc Dihydrospiro[benzo[1,2-b:5,4-b,]difuran-3,3W,dodol,(2Ή)-yl)propanal (1.74 g '87%) : MS (ES+) — 336Λ (M + 1) 〇 Example 15.1 Γ-{3-[(3-methylbutyl)amino]propyl b 5,6-dihydrospiro [benzo[12:5:7,7] Furan-3,3'-吲哚]々'(ΓΗ), synthesis of hydrochloride

3-(2-keto-5,6-one snail [benzo[l,2-b: 5,4-b,] diterpene-3,3^丨嗓Η, (2Ή)- Base) C-way (0.34 g, 1.00 mmol) with isoamylamine (〇2〇 ml, 143924-sp-20091127-5 -857- 201020257 1.72 mmol) in 1,2-dioxaethane (20 To the solution in ML), sodium triethoxysulfonate hydride (0.43 g, 1.92 mmol) was added. The reaction mixture was stirred at ambient temperature for 18 hours. The reaction was quenched with saturated sodium bicarbonate solution and extracted with hexane. The combined organic solution was washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was subjected to column chromatography &lt;RTI ID=0.0&gt;&gt;&gt; _mercaptobutyl)amino]propyl}_5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-4 哚]-2, ( 1 Ή)-ketone (0.37 g, 91%). Then 'transformed to its hydrochloride salt (〇36 g) by treatment with hydrogen chloride (2 Μ solution in diethyl ether, 〇5 mL, 1.0 mmol): mp 98-101 ° C (diethyl ether); Hidden (30〇]^1^,〇]^0-06)&lt;5 8.79〇^8,211),7.32-7.03 (m, 4H), 6.49 (s, 1H), 6.38 (s, 1H), 4.71 ( ABq, 2H), 4.49-4.43 (m, 2H), 3.82-3.65 (m, 2H), 2.94-2.82 (m, 6H), 2.00-1.96 (m, 2H), 1.60-1.41 (m, 3H), 0.83 (d, J = 9 Hz, 6H); MS (ES+) m/z 407.2 (M + 1). Example 15.2 l'-{3-[Butyl(methyl)amino]propyl}-5,6-dihydrospiro[benzo[12_b:5,4-b,]difuran-3,3. Synthesis of 卜多]-2'(1Ή)-ketohydrochloride

According to the procedure as described in Example 15.1, and irrelevant changes were made, the isoamylamine was replaced with Ν-methylbutylamine to obtain Γ_{3_[butyl(methyl)amino]propane 143924-sp*20091127- 5 - 858- 201020257 }}-5,6-monohydrospiro[benzo[i,2-b: 5,4-1&gt;'] bismuth _3,3Ί 嗓]-2,(1Ή)-ketone Hydrochloride (80%) 'is a colorless solid: refining point 96-99 ° C (ether); 1 η 尺 (3〇〇ΜΗζ, DMSO-d6) c5 10.5 (br s, 1H), 7.35-7.00 ( m, 4H), 6.49 (s, 1H), 6.37 (s, 1H), 4.71 (ABq, 2H), 4.49-4.43 (m, 2H), 4.15 (br, 1H), 3.82-3.73 (m, 2H) , 3.12-2.89 (m, 6H), 2.69-2.63 (m, 2H), 2.12-1.97 (m, 2H), 1.66-1.52 (m, 2H), 1.32-1.20 (m, 2H), 0.85 (U = 6.0 Hz, 3H) ; MS (ES+) m/z 407.2 (M + 1). Example 15.3 1 -{3-[(2'2,2-Difluoroethyl)amino]propyl 5-(6b:5 4b, Synthesis of 3,3'-啕嗓]-2'(1Ή)-ketohydrochloride

According to the procedure as described in Example 15.1, and irrelevant changes were made, the isopentenylamine was replaced with 2,2,2-trifluoroethylamine to obtain Γ·{3_[(2,2,2_5fluoroethyl)fluorene. Amino]propyl}-5,6-dihydrospiro[benzo[l,2-b:5,4?']difuran-3,3'-W哚]-2'(1Ή)-keto salt Acid salt (86%) as a colorless solid: m.p. 124-126: (ethyl ether); 1H NMR (300 MHz, DMSO-d6) 5 7.35-7.29 (m,1 Η), 7.21 - 7.12 (m, 2 Η), 7.06 -7.01 (m, 1H), 6.48 (s, 1H), 6.37 (s, 1H), 4.71 (AB, 2H), 4.49-4.43 (m, 2H), 4.06-3.97 (m, 2H), 3.87-3.70 (m, 2H), 3.04-2.89 (m, 4H), 2.11-2.00 (m, 2H); 13C NMR (75 MHz, DMSO-de) δ 111.6, 161.6, 161.1, 142.6, 132.7, 129.2, 124.1, 123.4 , 120.9, 120.3, 119.5, 92.9, 80.3, 72.5, 57.3, 46.0, 37.5, 28.8, 24.3, 22.5, 14.4; MS (ES+) m/z 419.1 (M + 1) » 143924-sp-20091127-5 • 859 - 201020257 Example 15.4 3-{[3-(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-W Synthesis of 嗓]-1'(2Ή)-yl)propyl]amino}propionitrile hydrochloride

The 3-{[3-(2'-keto-5,6-dihydrospiro) was obtained by substituting 3-aminopropionitrile for isodecylamine according to the procedure described in Example 15.1 and performing insignificant changes. [Benzo[l,2-b: 5,4-b']difuran-3,3'-indole]-indole (2Ή)-yl)propyl]amino}propanenitrile hydrochloride (61%) , as a colorless solid: mp 214-216 ° C (diethyl ether); 1H NMR (300 ΜΗζ, DMSO-d6) δ 7.33-7.29 (m, 1 Η), 7.20-7.12 (m, 2 Η), 7.04-6.99 (m ,1Η), 6.45 (s, 1H), 6.37 (s, 1H), 4.65 (ABq, 2H), 4.49-4.43 (m, 2H), 3.82-3.69 (m, 2H), 3.01-2.76 (m, 8H ), 1.92-1.79 (m, 2H); 13C NMR (75 MHz, DMSO-d6) δ 177.5, 161.6, 161.1, 142.8, 132.7, 129.2, 124.1, 123.4, 121.0, 120.3, 119.4, 109.5, 92.9, 80.2, 72.5, 57.3, 45.4, 43.6, 37.8, 28.8, 25.8, 16.2; MS (ES+) m/z 390.1 (M+ 1). Example 16 446-(Diammonium)pyridin-3-yl]-l'-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-di argon [benzo[1,2:7: Synthesis of 5,4 7 1 1 furan-3,3'-啕哚]-2'(1 ugly)-ketone 143924-SP-20091127-5 -860- 201020257 η3ο, νχη:

2-(dimethylamine anthracidine 5-dihydroxyborane hydrate (〇8 g [l,: ,0.45 mmol]),

Heat and stir in a microwave reactor for 15 minutes. The solution was poured into distilled water (15 ml) and washed with ethyl acetate (75 ml). The ethyl acetate layer was washed with brine (3×25 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash chromatography using ethyl acetate (gradient: 30% to 60%) to give 4'-[6-(dimethylamino)&gt; ]-r-[(2R)-Tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b : 5,4-b'] φ dipyran _3,3 '-吲嗓&gt;2'(1Ή)-one (0.11 g, 73%) as colorless solid: iHNMR (300 MHz, DMSO-d6) δ 7.53 (d, J = 2.4 Hz, 1H), 7.33 (dd , J = 7.8 Hz, 1H), 7.18 (dd, J = 7.4, 4.7 Hz, 1H), 6.77 (d, J = 7.2 Hz, 1H), 6.71 (ddd, J = 8.8, 2.4, 0.9 Hz, 1H) , 6.51 (d, J = 5.6 Hz, 1H), 6.31 (d, J = 8.8 Hz, 1H), 6.12 (d, J = 0.9 Hz, 1H), 4.59-4.41 (m, 3H), 4.33 (dd, J = 9.4, 3.1 Hz, 1H), 4.23-4.08 (m, 1H), 3.89-3.55 (m, 4H), 3.09-2.86 (m, 2H), 2.95 (s, 6H), 2.05-1.69 (m, 3H), 1.67-1.51 (m, 1H); MS (ES+) m/z 484.1 (M + 1). Example 16.1 143924-sp-20091127-5 •861 - 201020257 44(E)-2-(4-Fluorine Phenyl)vinyl H, _[(2R)_rahydrofuran-2-ylhydrazino&gt; 5,6-di-argon[benzo[l,2-b:5,4,7,]difuran_3 ,3,_吲哚]-2,(1Ή)-ketone synthesis

Displacement of 2-(diamino)pyridinium 5-dihydroxyboron using trans-2-(4-fluorophenyl)vinyldihydroxyborane according to the procedure as described in Example 16 and subject to insignificant changes Alkane hydrate, obtaining 4,_[(Ε)_2_(4_fluorophenyl)vinyl]- l'-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzene And [1,2-b: 5,4-b,]difur &quot;South-3,3'-吲哚]-2'(1Ή)-one (47%) as colorless solid: NMR (300 MHz , DMSO-d6) δ ΊΜ-Ί.25 (m, 4Η), 7.24-7.06 (m, 4H), 6.75 (d, J = 16.4 Hz, 1H), 6.52 (s, 1H), 6.48 (s, 1H ), 4.78 (ABq, J = 26.1, 9.6 Hz, 2H), 4.52-4.36 (m, 2H), 4.23-4.09 (m, 1H), 3.90-3.54 (m, 4H), 2.92 (t, J = 8.51 , 8.51 Hz, 2H), 2.04-1.69 (m, 3H), 1.68-1.53 (m, 1H); MS (ES+) m/z 484.1 (M + 1). Example 16.2 Heart dibenzo[b,d]porphin-4-yl-l'-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2- b: Synthesis of 5,4-b·]difuran-3,3'-呻哚]-2,(1Ή)-one

143924-sp-20091127-5 -862 201020257 Following the procedure as described in Example 16, and performing irrelevant changes, replacing 2-(diamine) with dibenzo V»cephen-4-dihydroxyborane Pyridine 5-dihydroxy benzene hydrate hydrates to obtain 4'-dibenzo[b,d&gt;cephen-4-yl-1,-[(2R)-tetrahydrop-pentan-2-ylmethyl] -5,6-dihydrospiro[benzo[i,2-b: 5,4-7,]difuran-3,3W丨哚]-2,(1Ή)-one (45%), as a colorless solid: 1 η NMR (300 MHz, DMSO-d6) (diastereomer) 5 8.53-8.02 (111,211), 8.02-7.70 (111,111), 7.67-7.21 (111,511), 7.20-6.91 (in, 2H), 6.59 (s, 0.5H), 6.19 (s, 1H), 5.96 (s, 0.5H), 5.28 (s, 0.5H), 5.01-4.76 (m, 0.5H), 4.68-4.31 (m, 2H), 4.29-4.13 (m, 1H), 4.11-3.52 (m, 5H), ® 3-20-2.67 (m, 2H), 2.13-1.71 (m, 3H), 1.71-1.50 (m , 1H) ; MS (ES+) m/z 546.0 (M + 1). Example 16.3 4'-(l-Benzosulfonyl-3-yl)_1'_[(2 ft)_tetrahydrofuran-2-ylmethyl]_5 6_di argon [benzo[l,2-b: Synthesis of 5,4-b']difuran-3,3'-吲哚]-2,(1Ή)-嗣

Following the procedure as described in Example 16, and performing an insignificant change, the use of a sulfur ring-like -3-diuretic shed to displace 2-(dimethylamino) ρ than a 5-di- sulphate hydrate , 4'-(1-benzothiophen-3-yl)_i'_[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]difuran-3,3,-anthracene-2,(1Ή)-one (49%) ' is a colorless solid: iHNMR (3 〇〇MHz, DMSO-d6) 5 7.86 (d , J = 7.2 Hz, 1H), 7.57-6.70 (m, 7H), 6.48-6.31 (br s, 1H), 5.76 (br s, 1H), 4.52-4.09 (m, 5H), 3.93-3.57 (m , 4H), 2.97-2.66 (m, 2H), 2.05-1.71 (m, 3H), 1.70-1.54 143924-sp-2009ll27-5 -863- 201020257 (m,1H) ; MS (ES+) m/z 496.1 (Μ + 1). Example 16.4 4'-(l-Mercapto-1H-indol-5-yl H4(2R)-tetrahydrofuran_2-ylindenyl]_5,6•dihydrospiro[benzo[l,2-b:5 Synthesis of 4,7']difuran-3,3'-&lt;哚]-2'(1Ή)-嗣

According to the procedure as described in Example 16, and the insignificant change was made, 1-mercapto-5-(4,4,5,5-tetradecyl-1,3,2-dioxaboron- 2-(2)-ih-W嗓 displaces 2-(monoamido)p to bite 5-di-based ruthenium hydrate to obtain 4'-(1-mercapto-1Η-ρ-p-wood-5-yl )-1 -[(2R)-tetradentate 〇南-2-ylindenyl]-5,6-dichlorospiro[benzo[l,2-b:5,4-b']difuran-3 , 3'-沔丨哚]-2.(1Ή)-ketone (65%) as a colorless solid: 1H NMR (300 MHz, DMSO-d6) δ 7.34 (dd, J = 7.8, 7.82 Hz, 1H), 7.26 (d, J = 3.0 Hz, 1H), 7.23-7.14 (m, 2H), 6.85 (d, J = 7.2 Hz, 1H), 6.73-6.71 (m, 1H), 6.63-6.57 (m, 2H) , 6.09 (d, J = 3.0 Hz, 1H), 6.03 (s, 1H), 4.62-4.46 (m, 2H), 4.40 (dd, J = 9.2, 2.7 Hz, 1H), 4.26-4.12 (m, 1H) ), 4.09 (dd, J = 9.2, 1.1 Hz, 1H), 3.92-3.56 (m, 4H), 3.79 (s, 3H), 3.16-2.90 (m, 2H), 2.04-1.71 (m, 3H), 1.69-1.54 (m, 1H); MS (ES+) m/z 493.2 (M + 1). Example 16.5 443,5-Bis(trifluoromethyl)phenyl]-l'-[(2R)--hydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2 Seven: 5,4 7 ']difuran-3,3'-啕哚]-2' (1 ugly)-ketone synthesis 143924-sp-20091127-5 •864· 201020257

Following the procedure as described in Example 16, and performing an insignificant change, replacing 2-(dimethylaminocyclopyridine 5-dihydroxyborane with 3,5-bis(difluoromethyl)phenyldihydroxyborane Hydrate, 4 L [3,5 bis(trifluoromethyl)phenyl η,-[(2r)_tetrahydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[12-7:5, 4,7,]difuran_3 3,_ Φ ten]-2,(1Ή)_嗣(40%) ' is a colorless solid: 4 NMR (300 MHz, CDC13)

δ 7.73 (s, 1Η), 7.36 (dd, J = 7.9, 7.9 Hz, 1H), 7.26-7.23 (m, 2H), 7.19 (dd, J = 7.2, 7.2 Hz, 1H), 6.83 (d, J = 7.7 Hz, 1H), 6.53 (s, 1H), 5.90 (s, 1H), 4.70 (d, J = 8.9 Hz, 1H), 4.51 (t, J = 8.9, 8.9 Hz, 2H), 4.39 (d , J = 9.1 Hz, 1H), 4.34-4.23 (m, 1H), 4.05-3.67 (m, 4H), 2.98 (t, J = 8.5 Hz, 2H), 2.15-1.83 (m, 3H), 1.79- 1.65 (m, 1H) ; MS (ES+) m/z 576.1 (M + 1). Example 16.6 4'-(4-Phenoxyphenyl)-l'-[(2R)_tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[Benzo® [Ub:W]difuran Synthesis of -3,3,-吲哚]-2,(1Ή)-ketone

According to the procedure as described in Example 16, and the insignificant change was made, the p-phenoxyphenyl dihydroxyborane was substituted for 2-(dimethylamino) ρ to bite 5-two 143924-SP-20091127-5 • 865- 201020257 Hydroxyborane hydrate, obtaining 4'-(4-phenoxyphenyl)-l'-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzene And [i,2-b: 5,4-b,]difuran-3,3,-啕哚]-2·(1Ή)-one (35%) as a colorless solid: iHNMR (300MHz, DMSO-d6 5 7.42-7.30 (m, 3H), 7.22 (dd, J = 7.6, 4.3 Hz, 1H), 7.11 (dd, J = 7.4, 7.4 Hz, 1H), 6.95 (d, J = 8.4 Hz, 2H) , 6.82 (d, J = 7.6 Hz, 1H), 6.78-6.70 (m, 4H), 6.50 (d, J = 5.8 Hz, 1H), 6.03 (s, 1H), 4.54-4.33 (m, 4H), 4.25-4.10 (m, 1H), 3.90-3.55 (m, 4H), 3.08-2.83 (m, 2H), 2.05-1.70 (m, 3H), 1.68-1.54 (m, 1H); MS (ES+) m /z 532.1 (M+ 1) 〇 Example 16.7 4'-[4-(2-Methylpropoxy)phenylhydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[1, 2:7:5,4,7] Synthesis of difuran-3,3,-吲哚]-2,(1Ή)-ketone

Substituting p-(2-mercaptopropoxy)phenyl dihydroxyborane 2 (diamidoamine aziridine 5-dihydroxyborane) according to the procedure as described in Example 16 and performing an insignificant change Hydrate to give 4,_[4-(2-mercaptopropoxy)phenyl]-indole [[2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2- b: 5,4-b,]difuran-3,3'-...嗓]-2'(rH)-one (34%) as colorless solid: iH NMR (300 MHz, CDC13) δ 7.31 (dd, J = 7.8, 7.8 Hz, 1H), 7.08 (ddd, J = 10.3, 7.9, 0.9 Hz, 1H), 6.88 (d, J = 7.7 Hz, 1H), 6.71-6.62 (m, 4H), 6.58 (s , 1H), 6.18-6.15 (m, 1H), 4.68-4.48 (m, 3H), 4.39-4.23 (m, 2H), 4.07-3.57 (m, 6H), 3.13-2.92 (m, 143924-sp- 20091127-5 866- 201020257 2H), 2.14-1.81 (m, 4H), 1.80-1.66 (m, 1H), 1.00 (dd, J = 6.7, 1.2 Hz, 6H); MS (ES+)m/z 512.2 ( M + 1). Example 16.8 4-(4-Butoxy-based)_1'_[(2 ft.)-tetrachloro guano-2-yl-methyl]_5,6-dioxaspiro[Benzene

Synthesis of [l,2-b:5,4-b']difuran-3,3,-anthracene-2,(1Ή)-one, h3c ❿ according to the procedure as described in Example 16, and carried out Insignificant change, using 2-butyryl phenyl diacetate to replace 2-(dimethylamino)p than biting 5-dihydroxyborane hydrate to obtain 4,-(4-butoxybenzene) -1,-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3 ,- 哚 哚]-2,(1Ή)-one (34%), as a colorless solid: iH NMR (300 MHz, CDC13) 5 7.31 (dd, J = 7.8, 7.8 Hz, 1H), 7.14-7.03 (m , 1H), 6.88 (d, J = 7.7 Hz, 1H), 6.72-6.61 (m, φ 4H), 6.58 (s, 1H), 6.16 (s, 1H), 4.69-4.46 (m, 3H), 4.39 -4.23 (m, 2H), 4.09-3.56 (m, 6H), 3.14-2.92 (m, 2H), 2.14-1.82 (m, 3H), 1.81-1.65 (m, 3H), 1.55-1.40 (m, 2H), 0.96 (t, J = 7.3 Hz, 3H); MS (ES+) m/z 512.1 (M + 1). Example 16.9 4'-(4-Phenoxyphenyltetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3, Synthesis of 3,-吲哚]-2'(1Ή)-ketone 143924-sp-20091127-5 -867- 201020257

Following the procedure as described in Example 16, and performing an insignificant change, the replacement of 2-(dimethylamino)pyridine 5-dihydroxyborane hydrate with p-methoxyphenyl dihydroxyborane was obtained. -(4-methoxyphenyl)-l,-[(2R)-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b' ] 吱 -3 -3, 3% 3⁄4 卜 呆 ] -2, (1 Ή)-ketone (41%) ' is a colorless solid: iHNMR (300MHz, CDC13) ά 7.32 (dd, J = 7.8, 7.8 Hz, 1H) , 7.19 (dd, J = 7.2, 4.8 Hz, 1H), 6.78 (d, J = 7.1 Hz, 1H), 6.70-6.59 (m, 4H), 6.52 (d, J = 5.2 Hz, 1H), 6.11 ( s, 1H), 4.58-4.40 (m, 3H), 4.26-4.09 (m, 2H), 3.90-3.54 (m, 7H), 3.09-2.87 (m, 2H), 2.05-1.70 (m, 3H), 1.68-1.54 (m, 1H); MS (ES+) m/z 469.9 (M + 1). Example 16.10 4'-Pyrimidine-5-yl-r-[(2R)-izghydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4- b,] Synthesis of difuran_3,3,_啕哚]-2,(1Ή)-one

Following the procedure as described in Example 16, and performing an insignificant change, the pyridyl-5-dihydroxyborane was substituted for 2-(diamidino)pyridine 5-dihydroxyborane hydrate to obtain 4'-pyrimidine. -5-yl-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b]difuran-3, 3,-啕哚]-2,(1Ή)-_ (38%), colorless 143924-sp-20091127-5 -868- 201020257 Solid: iH NMR (300 MHz, CDC13) (5 9.08 (s, 1H) , 8.12 (d, J = 1.16 Hz, 1H), 7.38 (dd, J = 7.8, 7.8 Hz, 2H), 7.24-7.16 (m, 1H), 6.83 (d, J = 7.6 Hz, 1H), 6.58- 6.53 (m, 1H), 6.04 (s, 1H), 4.72 (dd, J = 9.3, 1.3 Hz, 1H), 4.63-4.46 (m, 2H), 4.39 (dd, J = 9.3, 1.3 Hz, 1H) , 4.35-4.23 (m, 1H), 4.06-3.65 (m, 4H), 3.01 (t, J = 8.6 Hz, 2H), 2.16-1.84 (m, 3H), 1.79-1.63 (m, 1H); MS (ES+) m/z 442.0 (M + 1). Example 16.11 Heart [6-(dimethylamino)P-pyridin-3-yl]-indole-{ [5-(trifluoromethyl)pyran-2 -yl]methyl}-β 5,6-dihydrospiro[benzo[l,2-b:5,47']difuran-3,3'-啕哚]-2'(1Ή)-one Synthesis

According to the procedure as described in Example 16, and irrelevant changes were made, using 4'-bromo-1'-{[5-(trifluoromethyl)pyran-2-yl]hydrazin-5,6 -Dihydrospiro[Benzene-[Wb:5,4-b']dipyran-3,3'-吲嗓]-2,(1Ή)-one substituted 4,-bromo-l'-[( 2R)-tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[p- and [i,2-b:5,4-b']difuran-3,3,-嗍哚]- 2·(1Ή)-ketone' obtains 4·-[6-(didecylamino)P-pyridin-3-yl]-indole-{[5-(trifluoromethyl)oxy-2-yl]anthracene }}-5,6-dihydrospiro[benzo[i,2-b:5,47']difuran-3,3,-accord]-2·(1Ή)-one (73%) ' It is a colorless solid: melting point 223_225. (: ; 1H NMR (300 MHz, CDC13) δ 7.82-7.77 (m, 1H), 7.32 (dd, J = 7.8, 7.8 Hz, 1H), 7.25-7.23 (m, 1H), 6.93 (dd, J = 16.6, 7.8 Hz, 2H), 6.78-6.71 (m, 1H), 6.65-6.58 (m, 1H), 6.53 (s, 1H), 6.44 (d, J = 2.5 Hz, 1H), 6.28-6.16 (m , 2H), 5.19 (d, J = 143924-sp-20091127-5 -869- 201020257 16.1 Hz, 1H), 4.78 (d, J = 16.2 Hz, 1H), 4.71 (d, J = 9.2 Hz, 1H) , 4.64-4.50 (m, 2H), 4.47 (d, J = 9.2 Hz, 1H), 3.07-2.97 (m, 8H); MS (ES+) mJz 548.0 (M + 1). Example 16.12

L'-[(5-Gas-2-nonylphenyl)indolyl]-4'-[6-(diamidoamine)p is more than indole-3-yl] snail [p-B-B-[2, Synthesis of 3-f][l,3]benzodioxol-7,3'-啕哚]-2'(1Ή)-_ in a round bottom flask (25 ml) equipped with a condenser, Filled with 4,-bromo-indenyl-[[5-carbyl-2-ρsecenyl)fluorenyl] sulphide 南N-[2,3-f][l,3]benzodioxan _7,3'-M Budu]-2'(1Ή)-嗣(0.18 g, 0.50 mmol), 6-(dimethylamino)&gt;biting _3_dihydroxyborane (0.084 g) , 0.75 millimolar) and bismuth (triphenylphosphine) palladium (9) (〇〇6 g '10 mol%). The flask was flushed with nitrogen for 5 minutes, then anhydrous dioxane (7 ml) and 2 Μ sodium carbonate were added. (0.5 ml). The reaction mixture was heated under reflux for 16 h then cooled to ambient temperature and solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (20 ml) 〇ml), brine (10 ml) washed 'dehydrated with anhydrous sodium sulfate, and transition. The filtrate was concentrated to dryness in vacuo. The residue was purified by flash column chromatography using hexanes Ethyl ester (70%), which gives ^-[(5-carbyl·2-thienyl)methyl]-4'-[6-(dimethylamino)ρbidin-3-yl]spiro[吱喃[2,3-f][l,3]benzo-oxo-cetene-7,3'-p5丨11]-2'(1Ή)-one (〇.1〇克, 70%) , as colorless solid: 143924-sp^20091127-5 -870-201020257 Melting point 215-218°C; 1H NMR (300 MHz, DMSO-d6) (5 7.54 (d, J = 2.0 Hz, 1H), 7.34 (dd , J = 7.8, 7.8 Hz, 1H), 7.22 (d, J = 7.2 Hz, 1H), 7.13 (d, J = 3.8 Hz, 1H), 6.98 (d, J = 3.8 Hz, 1H), 6.80 (d , J = 8.0 Hz, 1H), 6.74 (dd, J = 8.8, 2.5 Hz, 1H), 6.38 (s, 1H), 6.33 (d, J = 8.8 Hz, 1H), 6.20 (s, 1H), 5.93 (d, J = 18.0 Hz, 2H), 5.05 (ABq, 2H), 4.44 (ABq, 2H), 2.95 (s, 6H); 13 C NMR (75 MHz, DMSO-de) δ 177.5, 158.4, 156.0, 148.9, 147.1, 142.3, 142.0, 138.4, 137.6, 137.3, 129.6, 129.4, 128.2, 127.9, 127.1, 126.1, 122.1, 121.1, 109.0, 104.7, 102.8, 101.9, 93.7, 77.9, 58.2, 38.1, 31.2; MS ( ES+) m/z 534.1 (M + Φ 1), 532.2 (M + l). Example 16.13 14(5-Gas-2-pyrimenyl)fluorenyl HH3-indolyl) snail [吱,[2,3-f][l,3]benzodioxol-7, Synthesis of 3'-嘀哚]-2·(1Ή)-ketone

φ according to the procedure as described in Example 16.12, and insignificantly changing, using 3-furan dihydroxyborane to replace 6-(dimethylaminothiaridin-3-yldihydroxyborane' to obtain Γ-[( 5-oxo-2-pyrimenyl)indenyl]-4'-(3-furanyl)spiro[吱,[2,3-!][1,3]benzodioxolene-7 , 3'-&lt;^丨哚]-2'(1 ugly)-ketone (95%) as colorless solid: mp 166-168 ° C; 1H NMR (300 MHz, DMSO-d6) 5 7.57 (dd, J = 1.7, 1.7 Hz, 1H), 7.34 (dd, J = 7.9, 7.9 Hz, 1H), 7.20 (d, J = 7.2 Hz, 1H), 7.11 (d, J = 3.8 Hz, 1H), 7.04 ( s, 1H), 6.99-6.96 (m, 2H), 6.77 (s, 1H), 6.19 (s, 1H), 6.03 (dd, J = 1.7, 0.8 Hz, 1H), 5.93 (d, J = 2.7 Hz , 2H), 5.04 (ABq, 2H), 4.55 143924-sp-20091127-5 -871- 201020257 (ABq, 2H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.4, 156.2, 149.1, 143.8, 142.9, 142.0, 140.6, 138.4, 130.7, 129.6, 128.2, 127.7, 127.0, 125.6, 122.9, 120.8, 111.4, 109.3, 102.9, 102.0, 93.9, 77.6, 58.1, 39.1; MS (ES+) m/z 480.3 (M+1 ), 478.3 (M + 1). Example 16.14 446-(Dimethylamino)pyridin-3-yl]spiro[furo[2,3-f][l,3]benzene Wu won alkenyl -7,3'- dioxo indol] -2 '(1Ή) -_ Synthesis of

4'-Bromo-based spiro[吱,[2,3-f][l,3]benzodioxolene-7,3'-啕哚]-2'(1Ή)-one (1.00 g ' 2.78 millimolars), 6-(diamine-amine-aziridin-3-yldihydroxyborane (0.69 g, 4.17 mmol) and guanidine (triphenylphosphine) red (9) 1.32 g, 〇28 mmol To a suspension mixture of hydrazine, hydrazine-dimethylformamide (30 ml), was added 2 mL aqueous sodium carbonate (2.8 mL, 5.6 m.). The reaction mixture was refluxed for 3 hours. The solid was filtered and washed with ethyl acetate (4 mL). The filtrate was concentrated in vacuo to dryness. The residue was purified by column chromatography using ethyl acetate (20% to 50% gradient) to give 4,-[6-(diamino)pyridin-3-yl] snail. [吱吱[2,3-Sink 1,3] benzodioxolane _7,3,_吲嗓]-2'(1Ή), (0.60 g, 54%), as a white powder: melting point &gt;245°c (ethyl acetate); 1H NMR (300 MHz, DMSO-de) 5 10.69 (s, 1H), 7.59 (d, J = 2.4 Hz, 1H), 7.29 (dd, J = 7.8, 7.8 Hz, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.79-6.74 (m, 2H), 6.40-6.35 (m, 3H), 5.95 (d, J = 19.9 Hz, 2H), 4.52 (d , J = 9.3 Hz, 1H), 143924-sp-20091127-5 -872- 201020257 4.36 (d, J = 9.3 Hz, 1H), 2.99 (s, 6H) ; 13 C NMR (75 MHz, DMSO-d6) &lt;5 178.8, 157.9, 155.5, 148.1, 146.6, 142.2, 141.5, 137.0, 136.8, 129.8, 128.9, 124.4, 121.9, 121.2, 109.0, 104.2, 102.5, 101.3, 93.1, 77.5, 58.2, 37.6; MS (ES+ m/z 402.3 (M + 1) ° Example 16.15 Γ-Methyl-4K2-keto-2H-nonene-7-yl)-2,3-dihydrospiro[吱,[2,3-g Synthesis of [l,4]benzodioxanthene-8,3W丨哚]-2'(1Ή)-one

Following the procedure as described in Example 16, and performing an insignificant change, using 4'-based core methyl-2,3-dihydrospiro[吱,[2,3-phan[1,4]benzene And dioxanedecene-8,3. 5丨哚]-2'(1Ή)-ketone replacement 4·-bromo-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6 - Dihydrospiro[benzo[l,2-b:5,4-b'] diced: s--3,3,-呻嗓]-2,(1Ή)-one, and using 7-(4, 4,5,5-tetradecyl-1,3,2-dioxaborin-2-yl)-2-indole-2-one (Isihiyama et al., Shan and Leii. (1997) 38: 3447 -3450) Substituting 2-(diamidoamine)p to bite 5-di-boron-boron hydrate to obtain i-methyl- 4'-(2-keto-2H-nonene-7-yl) -2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene_8,3,_ 哚 哚]-2·(1Ή)-ketone (55 %) 'As an off-white solid: mp 228-229 ° C (hexane / ethyl acetate); 1H NMR (300 MHz, CDC13) 5 7.71-7.63 (m,1H), 7.42-7.36 (m, 1H), 7.32 -7.27 (m, 1H), 6.99-6.94 (m, 1H), 6.93-6.86 (m, 1H), 6.80-6.74 (m, 1H), 6.69-6.64 (m, 1H), 6.43-6.36 (m, 1H), 6.34-6.29 (m, 1H), 6.00-5.94 (m, 1H), 4.67-4.60 (m, 1H), 435-4.04 (m, 5H), 3.32 (s, 3H) ; 13 C NMR (75 143924-sp-20091127-5 -873- 201020257 MHz, CDC13) (5 177.5, 160.5, 155.3, 153.1, 145.0, 143.2, 143.1, 142.1, 138.3, 138.2, 129.8, 128.9, 126.9 , 124.8, 124.5, 121.1, 117.7, 117.1, 116.6, 111.2, 108.2, 98.8, 78.4, 64.5, 63.9, 58.3, 26.9; MS (ES+) m/z 453.8 (M + 1). Example 16.16 Γ-Methyl- 4'-(2-ketotetrahydropbi-l-yl)-2,3-dihydrospiro[吱南南[2,3-g][l,4] benzodioxanthene Synthesis of -8,3'-吲哚]-2'(1Ή)-嗣

4'-Bromo-indenyl-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-2,(1Ή)-ketone (1.00 g, 2.57 mmol), 2-tetrahydropyrrole (0.30 ml, 3.9 mmol), potassium carbonate (0.71 g, 5.1 mmol) and racemic -trans-hydrazine, Ν'-dimercaptocyclohexane-1,2-diamine (0.10 ml, 0.63 mmol) in degassed solution in dimethyl amide (20 ml) Copper 1 (〇% g '0.31 mmol). The mixture was incubated at 150 ° C under nitrogen for 48 hours, allowed to cool to ambient temperature &apos; diluted with ethyl acetate, and washed with 10% v/v KOH, water and brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate to give hydrazine-methyl-4'-(2-ketotetrahydropyrrolidyl)-2,3-dihydrospiro[吱? 2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-2,(1Ή)-one (0·28 g, 28%): melting point 256-258 °C (ethyl acetate / hexane); ^ NMR (300 MHz, CDC13) 5 7.38-7.32 (m, 1H), 6.90-6.87 (m, 1H), 6.78-6.76 (m, 1H), 6.44 (s , 1H), 6.23 (s, 1H), 4.84 (ABq, 2H), 4.18-4.06 (m, 4H), 3.34-3.24 (m, 143924-sp-20091127-5 -874- 201020257 4H), 2.56-2.27 (m, 3H), 1.98-1.80 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 177.1, 175.9, 155.6, 144.7, 143.9, 138.1, 135.5, 131.4, 130.3, 122.8, 119.8, 111.5, 108.5 , 98.8, 78.3, 64.5, 63.9, 57.7, 50.6, 30.6, 27.1, 18.8; MS (ES+) m/z 393.1 (M + 1). Example 16.17 Indole-indolyl-4'-hofolin-4-yl-2,3-dihydrospiro[B-pyrano[2,3-g][l,4]benzodioxanene-8 ,3'-吲哚]-2'(1Ή)-ketone synthesis

4'-Bromo-indenyl-indenyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-qiao ]-2'(1Ή)-ketone (1.00 g, 2.57 mmol), whollen (0.34 ml '3.9 mmol), third, sodium butoxide (0.45 g, 4.7 mmol) and 9, 9-Dimethyl·4,5-bis(diphenylphosphino)dibenzopyran (0 30 g, 〇52 mmol) added to the degassed solution in toluene (milk) (Diphenylmethyleneacetone) two (0) (0.24 g, 0.26 mmol). The mixture was stirred under reflux for 24 hours under nitrogen and cooled to EtOAc EtOAc. Concentrate the liquid in a vacuum. The residue was subjected to column chromatography and eluted with ethyl acetate/hexane (1/1) to give 1'-mercapto-4'·hofolin-4_2,3_dihydrospiro[ Furano[2,3-g][l,4]benzodioxanthene _8,3,-ρ 嗓]-2,(1Ή)-one (0.04 g, 4%): melting point 246- 249 ° C (ethyl acetate / hexane broad iH NMR (3 〇〇 MHz, DMS 〇 _d6) δ 7.35-7.29 (m, 1 Η), 6.94-6.87 (m, 2H), 6.42 (s, 1H), 6.17 (s, 1H), 4.75 (ABq, 2H), 4.14-4.02 (m, 4H), 3.30 (t, J = 4.2 Hz, 4H), 3.12 (s, 3H), 143924-sp-20091127-5 - 875 - 201020257 2.52-2.27 (m, 4H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.8, 155.6, 149.9, 144.7, 144.3, 137.6, 130.3, 127.1, 121.6, 117.1, 111.3, 106.4, 98.6, 77.8, 66.7, 64.6, 64.0, 57.7, 53.0, 27.0; MS (ES+) m/z 395.0 (M + 1). Example 16.18 1'-Methyl-4'-(2-ketopyridine-1(2H) -yl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-thirsty]-2'(1Ή)- Ketone synthesis

In 4'-bromo-indenyl-methyl-2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxanthene]-2'(1Ή) , _ (1.00 g, 2.57 mmol), 2-hydroxypyridine (0.49 g, 5.2 mmol), potassium carbonate (ι·ι〇克, 7.95 mmol) and 8-hydroxyporphyrin (0.15 g' 1.04 millimolar) Copper iodide (I) (〇.1 g, 0.52 mmol) was added to the degassed solution in the diterpenoid (3 ml). The reaction mixture was heated at 150 ° C for 72 hours, allowed to cool to ambient temperature, diluted with diclofenac, successively washed with 10% v/v hydroxide, water and brine, and dried over anhydrous sodium sulfate. 'And filter. The filtrate was concentrated in vacuo. The residue β was subjected to column chromatography and dissolved in ethyl acetate/hexane (1/1) to give 1,1-methyl-4·-(2-ketopyridine-1(2H)-yl) -2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one (0Ό2克, 3%): melting point 212-214 ° C (ethyl acetate / hexane); 4 NMR (300 MHz, CDC13) 5 7.99-7.96 (m, 1H), 7.57-7.50 (m, 1H), 7.38- 7.34 (m,1H), 6.88-6.76 (m,3H), 6.69-6.66 (m,1H), 6.18 (s, 2H), 4.73 (s, 2H), 4.11-4.01 (m, 4H), 3.28 ( 3H) ; 13 C NMR (75 MHz, CDC13) δ 1173, 155.3, 149.9, 144.5, 144.2, 139.0, 137.7, 129.9, 123.6, 143924-sp-20091127-5 876 (8) 201020257 118.9, 117.9, 111.6, 105.3, 98.7 , 78.9, 64.4, 63.7, 57.4, 27.0; MS (ES+) m/z 403.0 (M + 1). Example 16.19 4'-Amino-indole-methyl-2,3-dihydrospiro[Miso-[2,3_g][1,4]benzodioxene-8,3'-啕哚] -ΚΓΗ)-ketone synthesis

0 to 4'-bromomethyl-2,3-dihydrospiro[furo-P,3-g][l,4]benzodioxanene-8,3'-吲哚]-2' (1Ή)-_ (11.58 g, 30.0 mmol), benzophenone imine (7.8 ml, 46 mmol) and racemic 2,2,_bis(diphenylphosphino)1,参 荇 (5.64 g, 9.00 mmol) in degassed solution in toluene (25 〇 ml), add gin (diphenylmethyleneacetone) dipalladium (9) (2·75 g, 3 〇〇 〇〇 Mohr), followed by sodium tris-butoxide (5.4 g, 56 2 mmol). The mixture was stirred under reflux with nitrogen for 20 h and filtered over a pad of Celite. The residue was dissolved in tetrahydrofuran (1 mL). 1% w/v salt acid (2 mL) was added and the mixture was stirred at ambient temperature for 5 hours and concentrated in vacuo to remove Most of the tetrahydrofuran was neutralized with 1% w/v aqueous sodium hydroxide solution and extracted with di-methane (3 χ 15 〇 ml). The combined organic extracts were washed with water and brine to dry sulfuric acid. Sodium dehydration drying, and filtration, concentrated in vacuum The filtrate was successively recrystallized from ethyl acetate/hexane followed by recrystallization from methanol to give 4,-amino-1,-methyl-2,3-dihydrospiro [biting and [2'3- g][l,4] stupid and diterpene terpene _8,3,_ρ!丨哚]_2, (1Ή) class (8 9 gram, 90%). melting point 252-254 ° C (acetate B Ester / hexane); NMR (300 ΜΗζ, • ΙΊΊ - 143924-sp-20091127-5 201020257 CDC13) δ 7.11-7.05 (m, 1H), 6.46 (s, 1H), 6.36-6.31 (m, 3H), 4.75 (ABq, 2H), 4.19-4.06 (m, 4H), 3.59 (br s, 2H), 3.23 (3H); MS (ES+) mJz 325.0 (M + 1). Example 16.20 N-(l'-曱-2'-keto-anthracene, 2,2',3-tetrahydrospiro[pf-rano[2,3_g][14]benzodioxanthene-8,3'-嘀哚]- Synthesis of 4^·yl)cyclobutanecarboxyxamide

4'-Amino-indole-methyl-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene-8,3'-呻哚]- 2'(1Ή)-ketone (700 mg, L72 mmol) in a solution of di-methane (50 ml) and bite (5 ml), adding cyclobutane gasified carbon 〇 at 〇 °c (0.17 ml, 1.48 mmol) ^ The reaction mixture was stirred at ambient temperature for 18 hours. Dilute with two gas (15 mL), and wash with water, 10% W/v hydrochloric acid, water and brine. Dehydrated and dried with anhydrous sodium sulfate, and transitioned. The agricultural condensate was filtered in a vacuum. The residue was subjected to column chromatography and eluted with ethyl acetate/hexane (1/3) to give Ν-(Γ-methyl-2,-keto-oxime, 2,2', 3-tetra Hydrogen ginseng bromine and [2,3-g][l,4]benzodioxanthene _8,3·- 哚]-4,-yl)cyclobutane decylamine (0.50 g) , 71%): melting point 234-236 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, DMSO-d6) (5 8.15 (s, 1H), 7.32-7.26 (m, 1H), 7.11- 7.08 (m, 1H), 6.94-6.91 (m, 1H), 6.43 (s, 1H), 6.17 (s, 1H), 4.68 (ABq, 2H), 4.13-4.05 (m, 4H), 3.15 (s, 3H), 2.96-2.90 (m, 1H), 2.05-1.64 (m, 6H); 13 C NMR (75 MHz, DMSO-dg) δ 176.6, 173.5, 155.1, 144.6, 144.3, 138.3, 134.6, 129.5, 125.3 , 120.8, 119.4, 112.0, 106.8, 98.8, 78.2, 64.6, 64.0, 57.1, 27.1, 25.0, 24.9, 143924-sp-20091127-5 - 878 - 201020257 17.9 ; MS (ES+) m/z 406,9 (Μ + 1) 〇 Example 16.21 Ν-(Γ-Methyl-2'-keto-oxime, 2,2',3-tetrahydrospiro[唉,[2,3 g][1,4]benzoic Oxygen

According to the procedure as described in Example 16.20, and irrelevant changes were made, 环 环-(Γ-methyl-2 was obtained by replacing cyclobutane with carbonized hydrazine with 2_(trifluoromethyl)benzhydryl chloride. ·-keto-anthracene, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,3^5,Bu] 4·-yl)-2-(trifluoromethyl)benzamide (66%): mp 241-243 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 8.02-7.98 (m, 1Η), 7.74-7.70 (m, 1H), 7.62-7.56 (m, 2H), 7.41-733 (m, 2H), 7.28-7.23 (m, 1H), 6.76-6.73 (m, 1H) , 6.33 (s, 1H), 6.03 (s, 1H), 4.71 (ABq, 2H), 4.18-4.08 (m, 4H), 3.29 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 175.9, 165.7, 153.8, _ 145.0, 142.8, 139.4, 134.3, 131.9, 130.3, 130.0, 127.5, 126.7, 120.7, 118.0, 116.5, 112.1, 105.2, 99.3, 78.8, 64.5, 63.8, 57.2, 27.1 ; MS (ES+) m /z 497.0 (M + l). Example 16.22 Ν-(Γ-曱-yl-2'-keto-oxime, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene Synthesis of ene-8,3'-嘀哚]-4'-yl)methanesulfonamide

• 879- 143924-sp-20091127-5 201020257 Follow the procedure as described in Example 16.20 and perform irrelevant changes by replacing the cyclobutane chlorocarbonate with decane sulfonium chloride to obtain Ν-(1· -mercapto-2'-keto-anthracene, 2,2',3-tetrahydrospiro[,,[2,3-g][l,4]benzodioxanthene-8,3· -吲哚]-4'-yl)nonanesulfonamide (89%): mp 184-186 ° C (ethyl acetate /hexane); 1H NMR (300 MHz, CDC13) 5 7.34-7.25 (m, 2H), 6.75-6.71 (m, 1H), 6.61 (s, 1H), 6.56 (br s, 1H), 6.34 (s, 1H), 4.70 (ABq, 2H), 4.19-4.06 (m, 4H), 3.29 (s, 3H), 2.35 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 175.5, 154.1, 145.3, 143.2, 139.6, 133.9, 130.3, 121.1, 118.5, 114.9, 111.6, 105.2, 100.4, 78.7 , 64.4, 63.9, 57.0, 38·7, 27.1; MS (ES+) m/z 402.9 (M+l). Example 16.23 Ν-(Γ-曱-yl-2'--yl-l',2,3-,3-tetrahydrospiro[Octa[2,3-g][l,4]benzodioxanthene Synthesis of ene-8,3'-啕哚]-41-yl)cyclohexanecarboxamide

According to the procedure as described in Example 16.20, and irrelevant changes were made, cyclobutane carbon tetrachloride was used to replace cyclobutane gasified carbonium to obtain Ν-(Γ-mercapto-2'-keto-oxime, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-啕哚]-I-yl)cyclohexane Carboxylamidine (23%) · · Melting point 96-98t: (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) d 7.99-7.95 (m, 1H), 7.31-7.25 (m, 1H), 7.04 (br s, 1H), 6.67-6.64 (m, 1H), 6.53 (s, 1H), 6.34 (s, 1H), 4.74 (ABq, 2H), 4.21-4.10 (m, 4H), 3.26 (s , 3H), 2.04-1.69 (m, 11H); 13C NMR (75 MHz, CDC13) δ 176.3, 174.5, 154.4, 145.3, 142.8, 139.3, 135.1, 129.8, 119.1, 143924-sp-20091127-5 -880- 201020257 118.0, 115.8, 112.3, 104.2, 99.4, 78.6, 64.5, 63.8, 57.1, 46,7, 29·4, 29.0, 27.0, 25.6; MS(ES+)m/z435.0(M + l) 〇Example 16.24 Ν-(1'-Methylketo-oxime, 2,2\3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3' Synthesis of -吲哚]-4'-yl)cyclopentane Carboxamide

Following the procedure as described in Example 16.20, and carrying out an insignificant change, gasification of the carbonium with cyclopentanecarbonate in the presence of cyclobutanecarbonate affords] ΝΚΓ-methyl-2'-keto-oxime, 2, 2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-啕哚]-4'-yl)cyclopentanecarboxylate Indoleamine (52%): mp 196-198 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) 3 7.98-7.94 (m,1H), 7.30-7.24 (m,1H), 7.09 (br s, 1H), 6.67-6.64 (m, 1H), 6.53 (s, 1H), 6.32 (s, 1H), 4.74 (ABq, 2H), 4.20-4.09 (m, 4H), 3.26 (s, 3H), 2.45-2.39 (m, 1H), 1.89-1.51 (m, 8H); 13C ❿ NMR (75 MHz, CDC13) 5 176.2, 174.7, 154.3, 145.2, 142.7, 139.3, 135.1, 129.8, 119.2, 118.2 , 115.9, 112.2, 104.2, 99.4, 78.4, 64.5, 63.8, 57.1, 46.7, 30.1, 29.9, 27.0, 25.9 ; MS (ES+) m/z 421.1 (M + 1) ° Example 16.25 1^-(1|- Methyl-2|-family-1|,2,2',3-four wind snail [bite 0^弁[2,3-8][1,4]benzodioxanthene-8,3 .丨哚]-4'-yl) Synthesis of acetamide

143924-sp-20091127-5 -881 - 201020257 According to the procedure as described in Example 16.20, and irrelevant changes are made, the cyclodane is used to gasify the carbonium with acetyl chloride to obtain N_(1,_methyl _2,keto-anthracene, 2,2',3-tetrahydrospiro[furo[2,3_g][1,4]benzodioxanthene_8,3,_啕哚] winter base Acetamine (27%): melting point 182-184 ° C (ethyl acetate / hexane); old NMR (300 MHz, CDC13) δ 7.89-7.85 (m, 1H), 7.31-7.24 (m, 1H) , 7.14 (br s, 1H), 6.69-6.65 (m, 1H), 6.53 (s, 1H), 6.32 (br s, 1H), 4.74 (ABq, 2H), 4.19-4.10 (m, 4H), 3.27 (s, 3H), 1.95 (s, 3H); 13C NMR (75 MHz, CDC13) δ 176.0, 168.5, 154.0, 145.1, 142.6, 139.4, 134.7, 129.7, 119.9, 116.1, 112,1,104.5, 99.2, 78.6, 64.5, 63.8, 57.1, 27.0, 24.3; MS (ES+) m/z 367.0 (M + 1). Example 16.26 Ν-(Γ-曱-yl-2'-keto-oxime, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene Synthesis of ene-8,3'-呻哚]-4'-yl)cyclopropanecarboxamide

According to the procedure as described in Example 16.20, and irrelevant changes were made, the cyclopropane gasified carbonium was used to replace the cyclobutane gasified carbonium to obtain Ν-(Γ-methyl-2'-keto-oxime, 2,2·,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-4'-yl)cyclopropane Carboxylamidine (78%): melting point 266-268 ° C (ethyl acetate / hexane); H NMR (300 MHz, CDC13) 5 7.93-7.89 (m, 1H), 7.33 (br s, 1H), 7.28-7.23 (m, 1H), 6.67-6.63 (m, 1H), 6.53 (s, 1H), 6.33 (s, 1H), 4.77 (ABq, 2H), 4.20-4.10 (m, 4H), 3.27 ( s,3H),1.26-1.17 (m,1H),0.99-0.73 (m,4H); 13C NMR (75 MHz, CDC13) δ 176.1, 172.1, 154.1, 145.1, 142.6, 139.4, 135.0, 129.7, 119.4, 118.3, 116.0, 112.1, 104.5, 99.3, 78.5, 64.5, 63.8, 57.2, 143924-sp.20091127-5 -882- 201020257 27.0, 15.6, 8.1, 8.0; MS (ES+) m/z 393.0 (Μ + 1) . Example 16.27 Ν-(Γ-Methyl-21-keto-oxime, 2,2',3-tetrahydrospiro[N,3-g][1,4]benzodioxanthene-8J Synthesis of -吲哚]-41-yl)benzamide

φ According to the procedure as described in Example M.20, and insignificantly changing, the cyclodane gasified carbon hydrazine was replaced with benzamidine chloride to obtain Ν-(Γ-fluorenyl-2,-keto- Γ,2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,3,-mouth?丨嗓]-4'- Benzobenzamide (60%): melting point 192-194eC (ethyl acetate / hexazone); 4 NMR (300 MHz, CDC13) δ 8.21-8.18 (m, 1H), 7.76 (br s, 1H) , 7.63-7.59 (m, 2H), 7.53-7.32 (m, 4H), 6.73-6.70 (m, 1H), 6.46 (s, 1H), 6.38 (s, 1H), 4.80 (ABq, 2H), 4.17 -4.08 (m, 4H), 3.28 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 176.3, 165.4, 154.2, 145.2, 143.0, 139.4, 135.0, 134.0, 132.1, ® 130.0, 128.6, 127.0, 119.4 , 117.9, 115.9, 112.2, 104, 6, 99.8, 78.5, 64.5, 63, 8, 60.4, 57.2, 27.0; MS (ES+) m/z 428.9 (M + 1). Example 16.28 2-Methoxy-indole-(Γ-methyl-2'-keto-1·,2,2',3-tetrahydrospiro [bite and [2,3_g][i,4]benzene Synthesis of Dioxetine-8,3·-吲哚]-4'-yl)acetamide

143924-SP-20091127-5 -883 - 201020257 According to the procedure as described in Example 16.20, and insignificantly changing, the use of decyloxylated acetonitrile to replace cyclobutane gasified carbonium to obtain 2-oxo oxygen Base-Ν-(Γ-methyl-2'-keto-oxime, 2,2·,3-tetrahydrospiro[furo[2,3-g][l,4]benzodioxanthene -8,3'-吲哚]-I-yl) acetamidine (70%): mp 237-239 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) &lt;5 8.07 ( Br s,1H),7.98-7.95 (m,1H), 7.33-7.27 (m, 1H), 6.71-6.67 (m, 1H), 6.50 (s, 1H), 6.29 (s, 1H), 4.73 (ABq , 2H), 4.20-4.09 (m, 4H), 3.89 (ABq, 2H), 3.31 (s, 3H), 3.25 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 176.7, 168.2, 155.2, 145.1 , 143.4, 138.7, 134.0, 129.8, 119.4, 117.5, 116.2, 111.8, 104.8, 99.7, 78.1, 71.9, 64.5, 63.8, 59.1, 57.1, 26.9; MS (ES+) m/z 396.9 (M + 1). Example 16.29 Ν-(Γ-Methyl-T-keto-l',2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene Synthesis of dilute -8,3'-p5 pulo]-4'-yl) propylamine

According to the procedure as described in Example 16.20, and the insignificant change was made, gasification of hydrazine was used to replace the cyclobutane gasified carbon hydrazine to obtain N_(1,_mercapto-2·-keto-oxime, 2, 2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-啕哚]-4,-yl)propanamide 42%): melting point 224-226. (:(ethyl acetate/hexane); 4 NMR (300 MHz, CDC13) δ 7.93-7.90 (m, 1H), 7.31-7.23 (m, 1H), 7.09 (br s, 1H), 6.68-6.64 ( m, 1H), 6.52 (s, 1H), 6.32 (s, 1H), 4.73 (ABq, 2H), 4.20-4.08 (m, 4H), 3.31 (s, 3H), 3.27 (s, 3H), 2.28 -2.07 (m, 2H), 1.07 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDC13) δ 176.7, 172.2, 154.1, 145.1, 142.7, 139.4, 143924-sp-20091127-5 •884 - 201020257 134.8, 129.8, 119.7, 118.2, 116.1, 112.1, 104.3, 99.3, 78.5, 64.5, 63.8, 57.1, 30.6, 27.0, 9.2; MS (ES+) m/z 381.0 (Μ + 1). Example 16.30 Ν- (Γ-Methyl-2'-keto-1-,2,2',3-tetrahydrospiro[吱,卩,卩3-2][1,4]benzodioxanthene-8, Synthesis of 3'-啕哚]-4-yl)pentaamine

According to the procedure as described in Example 16.20, and carrying out irrelevant changes, gasification of ruthenium by gasification of pentylene was used to obtain hydrazine-(1·-methyl-2·-keto-oxime, 2 , 2&gt; tetrahydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3W|哚]-4'-yl)pentamidine (30%): 182-183°C (ethyl acetate/hexane); iHNMRQOO MHz, CDC13) δ 7.96-7.92 (m, 1H), 7.31-7.23 (m, 1H), 7.09 (br s, 1H), 6.68-6.64 (m, 1H), 6.52 (s, 1H), 6.33 (s, 1H), 4.74 (ABq, 2H), 4.19-4.10 (m, 4H), 3.27 (s, 3H), 2.19-2.05 (m, 2H) ), 1.55-1.45 (m, 2H), 1.32-1.22 (m, 2H), 0.88 © (t, J = 7.2 Hz, 3H) ; 13 C NMR (75 MHz, CDC13) d 176.1, 171.6, 154.2, 145.1 , 142.7, 139.4, 134.9, 129.8, 119.5, 118.2, 116.0, 112.2, 104.3, 99.3, 78.6, 64.5, 63.8, 57.1, 37.5, 27.3, 27.0, 22.2, 13.7; MS (ES+) m/z 409.0 (M + 1). Example 16.31 2,2--Mercapto-indole-(Γ-methyl-2·-keto-1',2,2',3-tetrahydrospiro[pf-f-[2,3-g][ l,4] Stupid and dioxane 圜-8,3Ί嗓]-4'-yl) Synthesis of propylamine 143924-sp-20091127-5 •885 · 201020257

Following the procedure as described in Example 16.20, and carrying out an insignificant change, replacing the cyclobutane gasified carbonium with trimethylammonium chloride to obtain 2,2-dimethyl-indole-(Γ-methyl) -2'-keto-1',2,2',3-tetrahydrospiro[ρ-mero[2,3-g][l,4]benzodioxanthene-8,3'- , 5丨哚]-4'-yl)propanamide (47%): mp 182-184. (: (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 7.87 (br s, 1H), 7.33-7.27 (m, 1H), 7.22-7.18 (m, 1H), 6.94-6.91 ( m, 1H), 6.43 (s, 1H), 6.22 (s, 1H), 4.70 (ABq, 2H), 4.15-4.01 (m, 4H), 3.15 (s, 3H), 0.97 (s, 9H) ; 13C NMR (75 MHz,

CDC13) accounted for 177.0, 176.7, 155.0, 144.7, 144.4, 138.3, 135.0, 129.6, 124.3, 120.2, 119.1, 112.2, 106.6, 99.1, 78.1, 64.6, 64·0, 57.1, 39.2, 27.3, 27.1; MS (ES+ ) m/z 409.0 (M + 1). Example 16.32 Ν-(Γ-曱-yl-2'-keto-oxime, 2,2',3-tetrahydrospiro[p-f-[2,3-g][i,4]benzodioxan

According to the procedure as described in Example 16.20, and irrelevant changes were made, the gasified ruthenium was replaced with a gasified hexanone to obtain Ν_(Γ_methyl-2'-keto-1',2, 2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-卩?丨哚]-4'-yl)hexidine Amine (67%): mp 151-153 ° C (ethyl acetate / hexane); iH NMR (300 143924-SO-20091127-5 201020257 MHz, CDC13) δ 7.96-7.92 (m, 1H), 7.31- 7.23 (m, 1H), 7.10 (br s, 1H), 6.68-6.64 (m, 1H), 6.52 (s, 1H), 6.32 (s, 1H), 4.74 (ABq, 2H), 4.20-4.09 (m , 4H), 3.27 (s, 3H), 3.21-2.02 (m, 2H), 1.56-1.47 (m, 2H), 1.30-1.23 (m, 4H), 0.86 (t, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDC13) δ 176.1, 171.6, 154.1, 145.1, 142.6, 139.4, 134.9, 129.8, 119.5, 118.2, 116.0, 112.2, 104.3, 99.3, 78.5, 64.5, 63.8, 57.1, 37.7, 31.3, 27.0 , 24.9, 22.3, 13.9; MS (ES+) m/z 423.0 (M+l). Example 16.33 ® Ν-(Γ-Methyl-2'-keto-l',2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodiox Synthesis of terpenyl-8,3'-anthracene

According to the procedure described in Example 16.20, and irrelevant changes were made, ❺ Cyclobutane was used to replace cyclobutane gasified carbonium to obtain Ν-(Γ-methyl-2·-keto-l',2 , 2',3-tetrahydrospiro [bito-[2,3-g][l,4]benzodioxolene-8,3,-吲哚]-4,-yl)heptanylamine (46%): melting point 123-124 ° C (ethyl acetate / hexane): 4 NMR (300 MHz, CDCI3) δ 7.96-7.92 (m, 1H), Ί 31-123 (m, 1H), 7.10 (br s, 1H), 6.68-6.64 (m, 1H), 6.52 (s, 1H), 6.32 (s, 1H), 4.74 (ABq, 2H), 4.19-4.05 (m, 4H), 3.27 (s, 3H) , 3.21-2.03 (m, 2H), 1.53-1.47 (m, 2H), 1.35-1.14 (m, 6H), O.B6(t, J = 7.2Hz, 3H); 13 C NMR (75 MHz, CDC13 ) δ 176.1, 171.7, 154.1, 145.1, 142.6, 139.3, 134.9, 129.8, 119.5, 118.2, 116.0, 112.2, 104.3, 99.3, 143924-sp-20091127-5 -8S7- 201020257 78.5, 64.5' 63.8, 57.1, 37.8 , 31.4, 28, 8, 27.0, 25.2, 22.4, 14.0; MS (ES+) m/z 437.1 (M + 1). Example 16.34

2-(2-decyloxyethoxy)-indole-(Γ-methyl-2,-keto-_r,2,2,,3_rahydrosiro[吱,[2,3-g][l , 4] benzodioxane decene _8, 3' _ 4 pulo] carbendamide synthesis according to the procedure as described in Example 16.20, and the implementation of irrelevant changes, using 2-(2-曱ethoxyethoxy)ethyl ruthenium chloride is substituted for cyclobutane to gasify carbon ruthenium to obtain 2-(2-decyloxyethoxy)-fluorene-(Γ-methyl-2·-keto-1, , 2,2,,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene -8,3·-吲嗓]-4'-yl)B Indoleamine (77%): melting point 122-123 ° C (ethyl acetate / hexane); 4 NMR (300 MHz, CDC13) (5 8.08 (br s, 1H), 7.85-7.81 (m, 1H), 7.33-7.26 (m, 1H), 6.72-6.68 (m, 1H), 6.46 (s, 1H), 6.26 (s, 1H), 4.78 (ABq, 2H), 4.18-4.06 (m, 4H), 3.99 ( ABq, 2H), 3.65-3.40 (m, 4H), 3.32 (s, 3H), 3.24 (s, 3H) ; 1 3 C NMR (75 MHz, CDC13) δ 176.7, 168.5, 155.1, 144.9, 143.4, 138.7 , 133.8, 129.8, 120.4, 117.9, 117.2, 111.7, 105.1, 99.6, 77.8, 71.7, 70.8, 64.5, 63.8, 58.9, 57.1, 26.9; MS (ES+) m/z 441.1 (M + 1). Example 16.35 1 -hexyl-3-(anthracene-fluorenyl) -2'-keto-anthracene, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3·-4哚Synthesis of -4·-yl)urea 143924-sp-20091127-5 -888- 201020257

4-Amino-1'-methyl-2,3_dihydrospiro[biting and [2 3 g][i(4) benzodioxan-8'3'-蚓哚]_2, (1Ή )-ketone (〇. 克, 1.00 mmol) in a stirred solution of 1,4-dioxane (20 ml), adding trimethyl chloroformate 咻 "m liter, L2 mM The reaction mixture was heated to ambient temperature for a period of 24 hours, then allowed to cool to ambient temperature and concentrated in vacuo. The residue was dissolved in THF (10 mL). Cool to 〇 it. Add n-hexylamine (0 Λ 0 mL, 3.0 mmol) and triethylamine (〇.7 〇 ml, 5. 〇 mmol). Allow the reaction mixture to warm to ambient temperature and stir for 24 hours. The residue is dissolved in ethyl acetate and washed with water (4×15 mL). The organic phase is dried over anhydrous sodium sulfate, filtered, and concentrated in air. Recrystallization from ethyl acetate / hexane to give hexyl-3-(indole-methyl-2.-keto-1',2,2',3-tetrahydrospiro[furo[2,3 -笆][1,4]benzodioxanthene Χ-8Χ ρ朵]-4'-base) hiding (0.2 94 g, 64%), pale brown solid: 154-155 ° C (ethyl acetate / hexane); 4 NMR (300 MHz, CDC13) &lt;5 7.78-7.75 (m, 1H), 7.30- 7.25 (m, 1H), 6.63-6.60 (m, 1H), 6.52 (s, 1H), 6.34 (s, 1H), 6.09 (s, 1H), 4.76 (ABq, 2H), 4.22-4.11 (m, 5H), 3.28 (s, 3H), 3.14-3.00 (m, 2H), 1.48-1.41 (m, 2H), 1.32-1.25 (m, 6H), 0.89 (t, J = 6.7 Hz, 3H) ; 13C NMR (75 MHz, CDC13) δ 176.3, 154.6, 154.2, 145.1, 142.8, 139.4, 135.9, 129.8, 119.0, 118.3, 115.8, 112.2, 103.3, 99.3, 78.2, 64.5, 63.8, 143924-sp-20091127-5 - 889-201020257 57.1,40.5, 31.5, 29.8, 27.0, 26.4, 22.5, 14.0; MS (ES+) m/z 452.2 (Μ + 1). Example 16.36 1-cyclopentyl-3-(1-methyl-2 '-keto-anthracene, 2,2',3-tetrahydrospiro[pufrano[2,3_g][i,4]benzodioxanthene-8,3'-thirsty]-4 Synthesis of '-base' clothing

Following the procedure as described in Example 16.35, and carrying out irrelevant changes, replacing n-hexylamine with cyclopentylamine affords 1-cyclopentyl_3-(1,-methyl-2,-keto_1 ',2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanene·8,3,_(9)哚]-4,-yl) gland (61%) 'Yellow-yellow solid: melting point 133_135 〇c (ethyl acetate/hexane)·' 1H NMR (300 MHz, CDC13) &lt;5 7.76-7.73 (m, 1H), 7.31-7.25 (m, 1H), 6.63-6.60 (m, 1H), 6.52 (s, 1H), 6.34 (s, 1H), 6.07 (s, 1H), 4.77 (ABq, 2H), 4.20-4.11 (m, 5H), 3.81 -3.76 (m, 1H), 3.28 (s, 3H), 1.94-1.80 (m, 2H), 1.70-1.54 (m, 4H), 1.35-1.28 (m, 2H) ; 13C NMR (75 MHz, CDC13) &lt;5 176.3, 154.3, 145.2, 142.9, 139.3, 135.9, 129.8, 118.9, 118.3, 116.0, 112.3, 103.3, 99.2, 78.2, 64.5, 63.9, 57.1, 52.3, 33.6, 33.4, 27.0, 23.5, 23.5; MS (ES+) m/z 436.2 (M + 1). Example 16.37 1-Cyclohexyl-3-(anthracene-methyl-2'-keto-oxime, 2,2,,3-tetrahydrospiro [bito-and-[2,3-g][l,4]benzene Synthesis of Dioxetine-8,3'-吲哚]-4'-yl) Pulse

143924-sp-20091127-5 •890- 201020257 Following the procedure as described in Example 16.35, and carrying out irrelevant changes, replacing n-hexylamine with cyclohexylamine gives 1-cyclohexyl-3-(Γ-曱-2-2·-keto-1',2,2·,3-tetraspiro[吱,[2,3-g][l,4]benzodioxanthene-8,3W丨哚]-4,-yl)urea (57%) as colorless solid: mp 175-177 ° C (ethyl acetate); 1HNMR (300 MHz, CDC13) 5 7.72-7.69 (m, 1H), 7.30-7.24 ( m, 1H), 6.63-6.60 (m, 1H), 6.53 (s, 1H), 6.34 (s, 1H), 6.05 (s, 1H), 4.76 (ABq, 2H), 4.20-4.12 (m, 5H) , 3.41 (s, 1H), 3.28 (s, 3H), 1.90-1.82 (m, 2H), 1.71-1.58 (m, 3H), 1.41-1.01 (m, 5H) ; 13C NMR (75 MHz, CDC13) δ 176.3, 154.2, 153.9, 145.1, ❹ 142.9, 139.3, 135.9, 129.8, 119.3, 118.4, 116.1, 112.2, 103.3, 99.2, 78.3, 64.5, 63.8, 57.2, 49.2, 33.6, 33.5, 27.0, 25.5, 24.7; MS (ES+) m/z 450.1 (Μ + 1). Example 16.38 Ν-cyclohexyl-fluorenyl-fluorenyl-2'-keto-oxime, 2,2,3-trihydrospiro[吱,[2,3_g][i,4]benzo-infrared Synthesis of dilute -8,3·-ρ5|p]-4'-carboxy-decylamine

σ&quot; Γ Γ 曱-mercapto-2'-keto-l',2,2,,3-tetrahydrospiro[,4,3_g][1,4]benzodioxanthene- 8,3'-♦Duo]-4'-supplemented acid (0.200 g, 0.566 mmol) and iethyl_3 (3·diamidopropyl)-carbodiimide (0.114 g, 〇· 736 mM) ν,ν-diisopropylethylamine (0.30 ml, 1.72 mmol) and hydroxybenzotriene were added to the stirred solution in the dimethyl carbamide (20 ml). Azole (〇〇 92 g, 〇 68 mmol). The reaction mixture was stirred at ambient temperature for 1 min and cyclohexylamine (10 mL &lt;RTI ID=0.0&gt; The reaction mixture was stirred at ambient temperature for 40 hours&apos; and concentrated in vacuo to remove most of the ν, ν dimethyl s 143 s s s s s s s s s s s s s s s s s s The mixture was diluted with ethyl acetate (150 mL), washed with water (3········· The residue was purified by column chromatography and eluted with ethyl acetate / hexane (1/1) to give N-cyclohexyl fluorenyl 2, phenyl], hydrazine, 2, 2', 3- Tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene sparse_8,3,_4bdu]-4·-rebel amine (0.127 g '51%)' It is a colorless solid: melting point 139-140. (3;) HNMR (300 MHz, CDC13) δ 7.42-7.36 (m, 1H), 7.24-7.20 (m, 1H), 6.98-6.94 (m, 1H), 6.51 (s, 1H), 6.17 (s, 1H), 5.30-5.27 (m, 1H), 4.95 (ABq, 2H), 4.24-4.04 (m, 4H), 3.71-3.61 (m, 1H), 3.26 (s, 3H), 1.78-1.57 (m, 5H), 1.36-1.22 (m, 2H), 1.12-0.99 (m, 1H), 0.89-0.82 (m, 2H); 13 C NMR (75 MHz, CDC13) δ 177.6, 166.3, 155.9, 145.0, 144.3, 137.9, 134.7, 129.5, 127.4, 122.8, 120.4, 110.7, 109.9, 100.1.78.0, 64.5, 64.0, 58.2, 48.7, 32.4, 32.1, 26.7, 25.5, 24.9, 24.7; MS (ES+) m/z 435.0 (M + 1) 〇 Example 16.39 N-cyclopentyl-fluorenyl-fluorenyl-2'-keto-oxime, 2,2',3-tetrahydrospiro[vf-f-[2,3-g][l, 4] Synthesis of benzodioxanthene-8,3'-吲哚]-4'-carboxamide

Following the procedure described in Example 16.38, and carrying out irrelevant changes, replacing cyclohexylamine with cyclopentylamine afforded N-cyclopentyl-indole-methyl-2,-keto-oxime, 2,2, 3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-蚓哚]_4,-carboxamide (28%) 'is colorless Solid: melting point 135-136. (:(ethyl acetate/hexane); 143924-sp-20091127-5 •892- 201020257 1H NMR (300 MHz, CDC13) δ 7.43-7.36 (m, 1H), 7.24-7.22 (m, 1H), 6.98 -6.95 (m, 1H), 6.50 (s, 1H), 6.17 (s, 1H), 5.38-5.36 (m, 1H), 4.95 (ABq, 2H), 4.20-4.06 (m, 5H), 3.26 (s , 1H), 1.92-1.78 (m, 2H), 1.52-1.49 (m, 4H), 1.13-0.93 (m, 2H); 13C NMR (75 MHz, CDC13) δ 177.6, 166.8, 155.9, 145.0, 144.3, 137.9, 134.6, 129.5, 127.3, 122.8, 120.5, 110.7, 109.9, 100.0, 78.9, 64.5, 64.0, 58.1, 51.5, 32.6, 32.4, 26.9, 23.9, 23.7; MS (ES+) m/z 421.1 (M + 1 Example 16.40 © N-cyclopropyl-1'-fluorenyl-2'-mercapto-1',2,2\3-tetrahydrospirobi[2,3$][1,4] Synthesis of benzodioxanthene-8,3·-吲哚]-4·-carboxamide

Υ Following the procedure described in Example 16.38, and performing irrelevant changes, replacing cyclohexylamine with cyclopropylamine to obtain Ν-cyclopropyl-fluorenyl-indolyl-2·-keto-1|,2, 2',3-tetrahydrospiro[吱,[2,3$][1,4]benzodioxolene-8,3,-,5丨哚]-4,-carboxamide (36 %), as colorless solid: mp 127-128 ° C (ethyl acetate / hexanes); XH NMR (300 MHz, CDC13) δ 7.42-7.36 (m, 1H), 7.24-7.22 (m, 1H), 6.98 -6.96 (m, 1H), 6.52 (s, 1H), 6.17 (s, 1H), 5.41 (s, 1H), 4.90 (m, 2H), 4.21-4.11 (m, 4H), 3.26 (s, 3H ), 2.67-2.60 (m, 1H), 0.68-0.63 (m, 2H), 0.18-0.17 (m, 2H); 13C NMR (75 MHz, CDC13) δ 177.5, 168.5, 155.7, 145.1, 144.1, 137.9, 134.1, 129.6, 127.4, 122.9, 120.5, 110.6, 110.0, 100.1, 78.7, 64.6, 64.0, 58.0, 26.9, 22.8, 6.4, 6.2; MS (ES+) m/z 415.0 (M + 23). Example 16.41 143924-sp-20091127-5 •893- 201020257 1·-Indolyl (tetrahydropyrrol-1-ylcarbonyl)-2,3-dihydrospiro[吱,[2,3-g][l ,4] Synthesis of benzodioxanthene-8,3'-吲哚]-2Χ1Ή)-one

Following the procedure described in Example 16.38, and carrying out irrelevant changes, replacing the cyclohexylamine with tetrahydropyrrole to obtain 1,-methyl-4'-(tetrahydropyrrole-1-ylcarbonyl)-2,3- Dihydrospiro 1&gt; Furano[2,34][1,4]benzodioxanthene-8,3,-啕哚]-2'(1Ή)-one (8%) as a colorless solid : melting point 242-244 ° C (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 7.36-7.30 (m, 1H), 6.92-6.89 (m, 2H), 6.45 (s, 1H), 6.21 (s, 1H), 5.01 (ABq, 2H), 4.22-4.01 (m, 4H), 3.49-3.40 (m, 1H), 3.29 (s, 3H), 3.21-3.11 (m, 1H), 3.02- 2.93 (m, 1H), 2.43-2.35 (m, 1H), 1.77-1.62 (m, 3H), 1.39-1.29 (m, 1H) ; 13C NMR (75 MHz, CDC13) δ 177.6, 166.7, 156.2, 144.6 , 143.4, 137.5, 135.4, 129.1, 128.4, 120.4, 119.8, 111.1, 108.6, 99.0, 79.5, 64.6, 64.0, 58.2, 48.0, 44.9, 26.9, 25.5, 24.4; MS (ES+) m/z 407.0 (M + 1). Example 16.42 Γ-Methyl-2'-keto-N-pentyl-1·,2,2,,3-tetrahydrospiro[吱,[2,3-g][l,4]benzoic

According to the procedure described in Example 16.38, and irrelevant changes were carried out, 143924-sp-20091127-5 -894-201020257, replacing cyclohexylamine with n-pentylamine to obtain a fluorenyl-fluorenyl-2'. -N-pentyl-1|,2,2|,3-tetrahydrospiro[吱,[2,3$][1,4]benzodioxene-8,3|-啕哚] -4,-Carboxylimidamine (29%) as a pale yellow solid: m.p. 191-193. (ethyl acetate/hexanes); 1H NMR (300 MHz, CDC13) &lt;5 7.42-7.36 (m, 1H ), 7.24-7.22 (m, 1H), 6.99-6.95 (m, 1H), 6.50 (s, 1H), 6.20 (s, 1H), 5.32-5.25 (m, 1H), 4.92 (ABq, 2H), 4.21-4.09 (m, 4H), 3.30-3.17 (m, 1H), 3.27 (s, 3H), 3.06-2.95 (m, 1H), 1.30-1.11 (m, 6H), 0.87 (t, J = 7.1 Hz, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.6, 167.0, 155.8, 145.0, 144.1, 137.9, 134.4, 129.5, 127.8, 122.9, 120.6, 110.7, 109.9, 99.8, 78.8, 64.5, 64.0, 58.1 , 39.9, 29.0, 28.7, 26.9, 22.3, 13.9; MS (ES+) m/z 423.1 (M + 1). Example 16.43 N-(2-decyloxyethyl)-1·-methyl-2'-keto-oxime, 2,2·,3-tetrahydrospiro[吱,[2,3-g][ Synthesis of O, 4, benzodioxanthene-8,3,-bend]-4,-carboxamide

N-(2-methoxyethyl)-r-methyl-2'- was obtained by substituting 2-methoxyethylamine for cyclohexylamine according to the procedure described in Example 16.38. Keto-anthracene, 2,2',3-tetrahydrospiro [bito-and-[2,3-g][l,4]benzodioxanthene•8,3·-吲p]-4 '-Carboxyguanamine (14%), colorless solid: mp 97-100. (: (ethyl acetate / hexane); 111 匪 11 (300 questions 2, € 〇 (: 13) 5 7.41-7.36 (111, 1 printed, 7.21-7.18 (m, 1H), 6.99-6.96 (m, (H, 1H) ; 13 C NMR (75 ri..\v· 143924-sp-20091127-5 - 895 - 201020257 MHz, CDC13) δ 177.8, 167.2, 155.9, 144.8, 144.1, 137.8, 134.0, 129.4, 128.4, 122.4, 120.4, 110.8, 110.0, 99.4, 79.0, 70.9, 64.5, 63.9, 58.6, 58.3, 39.4, 26.9; MS (ES+) m/z 411.0 (Μ + 1). Example 16.44 N-(4-fluorobenzyl)-Γ- Mercapto-2·-keto-1,2,2',3-tetrahydrospiro[吱,[2,3-g][l,4] benzodioxene-8,3^ 5丨哚: Synthesis of K-carboxyguanamine

Following the procedure described in Example 16.38, and carrying out an insignificant change, the cyclohexylamine was replaced with 4-fluorobenzylamine to give the indole-(4-fluorobenzyl)-indole-methyl-2'-keto- Bismuth, 2,2',3-tetrahydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3,-thirsty]-4'-carboxamide (13%) as colorless solid: m.p. 149-150°C (ethyl acetate/hexane); 4 NMR (300 MHz, CDC13) &lt;5 7.43-7.38 (m,1H), 7.30-7.27 (m, 1H), 7.08-6.93 (m, 5H), 6.43 (s, 1H), 6.14 (s, 1H), 5.56-5.53 (m, 1H), 4.96 (ABq, 2H), 4.53-4.46 (m, 1H) , 4.20-3.93 (m, 5H), 3.27 (s, 1H) ; 13C NMR (75 MHz, CDCI3) δ 177.5, 166.9, 163.8, 155.7, 144.9, 144.2, 137.9, 133.7, 133.3, 129.9, 129.8, 129.6, 128.2, 123.0, 120.3, 115.6, 115.3, 110.6, 110.3, 99.7, 78.9, 64.4, 63.8, 58.2, 43.4, 26.9; MS (ES+) m/z 461.0 (M + 1). Example 16.45 N-Hexyl-fluorenyl-methyl-2·-keto-1,2,2,3-trihydrospiro[smog[2,3-g][l,4] stupid and dioxo Synthesis of urinyl-8,3'-啕哚]-4'-treazone 143924-sp-20091127-5 •896- 201020257

Γ-Γ-yl-2'--yl_1',2,2',3-tetrahydrospiro[吱,[2,3$][1,4]benzodioxanene-8, 3,-啕哚]-4·-carboxylic acid (0.200 g, 0.566 mmol) in a stirred solution of hydrazine, hydrazine-dimercaptocaramine (12 ml), adding hydroxybenzotrisole_ (0.151 g, 1.13 mmol), bismuth tetrafluoroborate _(benzotriazol_1_yl)_1^^,, 1^ tetradecyl fluorene (0.364 g, 1.13 mmol) and hydrazine, hydrazine- Diisopropylethylamine (0.81 ml '4.5 mmol). The reaction mixture was stirred at ambient temperature for 15 min, and n-hexylamine (0.15 mL, 1.1 mmol) was then stirred at ambient temperature for 72 s. and concentrated in vacuo. Ethyl acetate was washed with water (3 X 150 ml), 1 NaOH aqueous solution (2 Χ 1 mL) and brine (2×100 mL). The organic layer was dried over anhydrous sodium sulfate and evaporated. Concentration. The residue alkane/ethyl acetate is recrystallized into φ crystals to give Ν-hexyl-fluorenyl-methyl-2'-keto-oxime, 2,2,3-trihydrospiro[furan[2 , 3-g][l,4]benzodioxanthene-8,3'-indole; anthracene-carboxyguanamine (0.180 g, 73%), colorless solid: mp 172-173 ° C ( Ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) δ 7.42-7.36 (m, 1H), 7.26-7.22 (m, 1H), 6.99-6.96 (m, 1H), 6.49 (s, 1H) , 6.20 (s, 1H), 5.30-5.26 (m, 1H), 4.92 (ABq, 2H), 4.25-4.07 (m, 4H), 3.27-2.97 (m, 5H), 1.30-1.18 (m, 8H) , 0.87 (t, J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDC13) &lt;5 177.6, 167.0, 155.8, 145.0, 144.1, 137.9, 134.4, 129.5, 127.8, 122. 9, 120.6, 110.7, 109.9, 99.8, 78.8, 64.5, 64.0, 58.1, 40.0, 143924-sp-20091127-6 -897- 201020257 31.4, 28.9, 26.9, 26·5, 22.5, 14.0; MS(ES+)m /z437.1 (M + l). Example 16.46

Γ-Methyl Iketo-N-(p-pyridin-2-ylmethyl)-l,,2,2,,3-tetrahydrospiro[吱,[2,3-g][l,4 The synthesis of benzodioxanthene _8,3,_p?]哚]_4,_carboxamide was carried out according to the procedure described in Example 16.45, and the irrelevant change was carried out using 2-(aminomethyl) The anthraquinone is substituted with n-hexylamine to obtain Γ-mercapto-2, keto-indo-(pyridin-2-ylindenyl)-indole, 2,2,3-trihydrospiro[furo[2, 3-g][l,4] benzodioxanthene-8,3'-oxime]-4,-deacetamide (38%) as colorless solid: mp 214 215. ;4 NMR (300 MHz, CDC13) δ 8.46-8.44 (m,1H), 7.70-7.64 (m, 1H), 7.43-7.37 (m, 1H), 7.26-7.14 (m, 3H), 7.00-6.97 ( m, 1H), 6.62 (s, 1H), 6.30 (s, 1H), 6.16 (s, 1H), 4.97 (ABq, 2H), 4.66-4.31 (m, 2H), 4.11-3.90 (m, 4H) , 3.28 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 177.8, 167.2, 155.8, 155.7, 148.5, 144.5, 144.1, 137.7, 137.1, 133.9, 129.4, 128.9, 122.4, 122.3, 122.2, 120.4, 110.8 , 110.0, 99.2, 79.1, 64.3, 63.7, 58.4, 44.7, 26.9; MS (ES+) m/z 444.1 (M + 1). Example 16.47 N-(4-Fluorophenyl)-indole-indenyl-2' - -1',2,2',3-tetrahydrospiro[吱,[2,3-phan [1,4] benzodioxanthene-8,3'-吲哚M'-carboxyindole] Synthesis of amines 143924-SP-20091127-6 -898- 201020257

According to the procedure described in Example 16.45, and irrelevant changes were made, the n-hexylamine was replaced with 4-fluoroaminoamine to obtain N_(4-fluorophenyl)_1'-mercapto-2-indolyl-1'. ,2,2',3·tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-4·-❹ Rebel Amine (59%) 'as pale pink solid: melting point &gt; 250. (:(ethyl acetate/hexane); 1H NMR (300 MHz, DMSO-d6) d 10.00 (br s, 1H), 7.52-7.47 (m, 1H), 7.39-7.34 (m, 2H), 7.26- 7.20 (m, 2H), 7.12-7.06 (m, 2H), 6.21 (s, 1H), 6.13 (s, 1H), 4.85 (ABq, 2H), 4.13-3.91 (m, 4H), 3.21 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.6, 165.7, 158.7 (d, JC.F = 238.5 Hz), 156.1, 144.7, 144.2, 137.5, 135.4, 135.3, 134.5, 129.5, 128.8, 122.5, 122.4, 121.6, 120.1,

115.4 (d, JC.F = 21.8 Hz), 111.7, 110.8, 98.5, 79.8, 64.6, 64.0, 58.3, 27.1; MS (ES+) m/z 447.2 (M + 1) 实例 Example 16.48 4'-Amino -Γ-Pentyl-2,3-dihydrospiropyrano[2,3_g][1,4]benzodioxanthene-8'3''β哚]-2,(1Ή)-one Synthesis

According to the procedure described in Example 16.19, and with irrelevant changes, 4'-bromo-indolyl-pentyl-2,3-dihydrospiro[唉,[2,3_g][1,4]benzene was used. And dioxane 143924-sp-20091127-6 -899- 201020257 terpene-8,3'-啕哚]-2'(1 Ή)-ketone replacement 4'-bromo-indenyl-indenyl-2,3 -Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one, 4'-amino group -Γ-Pentyl-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxene-8,3Μ|哚]-2'(1Ή)-one (79%), as an orange solid: 4 NMR (300 MHz, CDC13) (5 7.11-7.05 (m, 1H), 6.48 (s, 1H), 6.36-6.32 (m, 3H), 4.78 (s, 2H ), 4.21-4.11 (m, 4H), 3.84-3.58 (m, 2H), 1.76-1.66 (m, 2H), 1.39-1.33, (m, 4H), 0.91 (t, J = 6.6 Hz, 3H) MS (ES+) m/z 380.9 (M + 1). Example 16.49 4'-(Y-Amino)-indole-{[3-(trifluoromethyl)-rhodin-2-yl]indolyl}-2 Synthesis of 3-dihydrospiro[吱, 并[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one

41-Bromo-indenyl-{[3-(trifluoromethyl)acridin-2-yl]methyl b 2,3-dihydrospiro[吱,[2,3-g][l,4 Benzodioxanthene _8,3,_啕哚]-2, (ΓΗ)-ketone (0.700 g, 〇1.31 mmol), ginseng (diphenylmethyleneacetone) dipalladium (9) (〇 14 g, 〇16 mmol, third-butyryl sodium (0.252 g, 2.62 mmol), 2,2,-bis(diphenylphosphino)-1'Γ-linked oxime (0.29 g, 0.47) Millol) and benzylamine (0.22 mL, 2.0 mmol) were combined in anhydrous toluene (20 mL) and taken to 105. (The next heating was carried out for 60 hours. The reaction mixture was filtered through a pad of Celite, and washed with ethyl acetate (15 mL). The filtrate was washed with saturated aqueous sodium hydrogen carbonate (1 mL), water (1) Washed with MgSO4 and brine (1 mL), dried over anhydrous sodium sulfate, filtered, </ </RTI> </RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> </ RTI> <RTIgt; And eluted with a gradient of 0% to 25% of ethyl acetate in dichloromethane to give 4,_((amino)H,_{[3-(difluoroindenyl)p than bit-2-yl] Methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-吲哚]-2, (1Ή&gt; ketone (0,227 g, 31%) as colorless solid: 1H NMR (300 MHz, CDC13) 5 8.67 (d, J = 4.5 Ηζ, 1 Η), 7.95 (d, J = 7.9)

Hz, 1H), 7.34-7.17 (m, 5H), 7.02 (d, J = 7.7 Hz, 1H), 6.95 (dd, J = 8.3, 8.3

Hz, 1H), 6.83 (s, 1H), 6.40 (s, 1H), 6.15 (ABq, 2H), 5.23 (ABq, 2H), 4.86 (ABq, 2H), 4.20-4.15 (m, 4H) 〇

Example 16.50 4'-Amino-indole-{[3-(trifluoromethyl)pyridine-2-yl]methyl b 23-dihydrospiro [bito-[2,3-g][l'4] Synthesis of benzodioxanthene _8,3'_byside]-2'(1Ή)-ketone

.Os ^ mouth

44 octylamino η'_{[3-(trifluorofyl)ρpyridin-2-yl]methyl}_2,3_dihydrospiro[吱,[2,3-g][l, 4] benzodioxanthene _8,3,_吲哚]_2, (1 Ή) ketone ketone, 0.45 millimolar) and palladium hydroxide / carbon (〇 251 g, 2 〇 anhydrous weight%, containing A mixture of ~50% water, 〇18 mmol, methanol (2 mM), glacial acetic acid dropwise, catalytic amount) was placed under a hydrogen atmosphere (1 atm) and stirred at ambient temperature for 16 hours. Further, add hydrazine to / carbon (9) gram, 2 〇 anhydrous weight%, containing ~ 50% water '0.072 mmol> with acetic acid (1 drop, catalytic amount of the reaction mixture once again placed in the hydrogen atmosphere (1 Under atmospheric pressure, and allowed to react at ambient temperature for 72 hours. The reaction mixture was passed through a diatomaceous earth pad, 143924-sp-20091127-6 -901 - 201020257 and washed with ethyl acetate (50 ml). The filtrate was washed with water (1 mL) and brine (100 mL). The organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo. The ester is dissolved in a 0% to 25% gradient in di-methane to give 4,-amino-indole-{[3-(trifluoromethyl; Kb-pyridine-2-yl)methyl}-2,3 - Dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8,3·-峋哚]-2'(1Ή)-one (0.070 g, 33% ), as a colorless solid: mp 243 _ 245 ° C; 1H NMR (300 MHz, DMSO-d6) 5 8.68 (d, J = 4.6 Hz, 1H), 8.25 (d, J = 7.9 Hz, 1H), 7.58 (dd, J = 7.7 Hz, J = 5.0 Hz, 1H), 6.91 (dd, J = 8.0 Hz, J = 8.0 Hz, 1H), 6.54 (d, J = 12.1 Hz, 1H), 6.33 (d, J = 8.2 Hz, 1H), 6.08 (d, J = 7.6 Hz, 1H), 5.14 (ABq, 2H), 4.71 (ABq, 2H)S 4.52 (s, 2H) , 4.17 (m, 4H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 154.9, 152.6, 152.4, 144.7, 142.9, 142.8, 138.8, 134.2, 134.1, 129.4, 122.0, 118.6, 114.5, 112.8, 111.3, 99.0 , 77.2, 64.5, 63.9, 57.2, 42.4 ; MS (ES+) m/z 469.9 (M + 1). Example 16.51 4·-Pheptyl-2,3-dihydrospiro[吱,[2,3-g Synthesis of [l,4]benzodioxanthene-8,3,_吲哚]-2·(1Ή)-one

4'-Bromo-1',2,2·,3-tetrahydrospiro[,,[2,3-g][l,4]benzodioxanthene -8,3M丨哚] (0.30 g, 0.80 mmol) in a solution of anhydrous tetrahydrofuran (2 mL), at -98 ° C, was added a third-butyl lithium (1.90 ml, 1.7 M in pentane) Solution, 3.2 mmol, and mix for 15 minutes. Trimethyl succinate (0.36 ml, 3.2 mmol) was added and the reaction mixture was allowed to warm to ambient temperature, 143924-sp-20091127-6-902-201020257

And mixing for 16 hours. At 0 C, a solution of hydrogen peroxide in water (〇·28 ml '35% w/w, 3.2 mmol) was added to the reaction mixture and the mixture was allowed to warm to ambient temperature 'mixed for 0.5 hour' And concentrated in a vacuum. The residue was triturated with water and filtered. The solid formed is purified by column chromatography and eluted with a gradient of 0% to 5% in ethyl acetate in dioxane to give 4'-hydroxy-2,3-dihydrospiro[吱Methyl [2,3-g][l,4]benzodioxanthene _8,3,-峋 ]]-2·(1Ή)-one (0.004 g ' 2%) ' is a colorless solid: Melting point &gt;25〇. H; iHNMR (300 MHz, DMSO-c^) 5 10.37 (s, 1H), 9.50 (s, 1H), 7.00 (dd, J = 8.0, 8.0 © Hz, 1H), 6.39-6.34 (m, 3H) , 6.08 (s, 1H), 4.64 (ABq, 2H), 4.09 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) d 179.3, 155.5, 154.1, 144.0, 143.6, 137.7, 130.1, 121.0, 116.1, 111.1, 110.5, 101.8, 98.7, 76.8, 64.6, 64.0, 57.2; MS (ES+) m/z 311.7 (M + 1). Example 16.52 4'-Phenyl-indole-methyl-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxene-8,3'-吲嗓]-2, (1 ugly)-ketone synthesis

According to the procedure as described in Example 16.51, and with irrelevant changes, 4'-bromo-1'-mercapto-2,3-dihydrospiro[furo[2,3-g][l, 4] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one substituted 4·-bromo-indole, 2,2',3-tetrahydrospiro[furan[2] , 3-phan[1,4]benzodioxanthene-8,3,-indole, obtaining 4|-hydroxy-1'-mercapto-2,3-dihydrospiro [biting and argon [2 ,3-g][l,4]benzodioxanthene-8,3'-峋哚]-2Χ1Ή)-one

(37%), as colorless solid: mp. &lt;250 °C; iHNMRPOOMHLDMSOO 143924-sp-20091127-6 • 903· 201020257 δ 9.61 (s, 1Η), 7.14 (dd, J = 8.0, 8.0 Hz, 1H), 6.56 (d, J = 7.7 Hz, 1H), 6.50 (d, J = 83 Hz, 1H), 6.40 (s, 1H), 6.12 (s, 1H), 4.67 (ABq, 2H), 4.17-4.09 (m , 4H), 3.12 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 177.0, 155.0, 153.3, 144.7, 143.6, 137.1, 129.6, 120.2, 114.6, 110.9, 110.8, 100.2, 98.1, 76.2, 64.1, 63.5, 56.3, 26.5; MS (ES+) m/z 325.8 (M + 1). Example 16.53 1'-Methyl-4·-indolyl-2-yloxy)-2,3-dihydrospiro[N,3-[2,3-g][l,4]benzodioxan Synthesis of octaene-8,3'-吲哚]-2'(1Ή)-ketone

4'-Hydroxy-indole-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-啕哚] -2'(1Ή)-ketone (0.120 g, 0.37 mmol), copper (I) (0.007 g, 0.04 mmol), potassium carbonate (0.066 g, 〇48 mmol), 2_bromo Pyridine (0.070 ml '0.74 mmol) and 1-butyl-1 oxime-imidazole (0.024 mL '0.18 mmol) were combined in anhydrous benzene (1 mL) and heated at 120 ° C in a sealed tube. 50 hours. Dichloromethane (25 mL) was added and the mixture was washed with water (3.times.25 mL). The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was triturated in methanol to give 1,1-methyl-4'-indolepyridin-2-yloxy)-2,3-dihydrospiro[吱,[2,3-g][l , 4] benzodioxanthene-8,3'-sideside]-2·(1Ή)-one (0.080 g, 54%), as colorless solid: mp 219-221 〇 C; 2H NMR (300 MHz, DMSO-d6) δ 7.91-7.89 (m, 1H), 7.67-7.62 (m, 1H), 7.35 (dd, J = 8.1, 8.1 Hz, 1H), 6.98-6.94 (m, 2H), 6.72 ( d, J = 8.3 Hz, 1H), 6.65 (d, J = 8.3 Hz, 1H), 6.11 (d, J = 10.4 Hz, 1H), 4.57 (ABq, 143924-sp-20091127-6 -904- 201020257 2H ), 4.10-3.93 (m, 4H), 3.18 (s, 3H); 13C NMR (75 MHz, DMSO-t^) δ 176.3, 162.4, 154.6, 149.4, 146.6, 144.7, 143.7, 139.5, 137.1, 129.8, 123.0, 118.9, 118.5, 117.3, 111.5, 110.6, 105.7, 97.9, 77.6, 64.0, 63.4, 56.5, 26.8; MS (ES+)m/z 403.2 (M + 1) 〇Example 16.54 4'-[2-(2 -decyloxyethoxy)ethoxy,-methyl-2,3-dihydrospiro[,,[2,3-g][l,4]benzodioxanthene _8,3 ·-叼丨哚]-2,(1Ή)-ketone synthesis

The 2-bromopyridine was replaced with 1-bromo-2-(2-methoxyethoxy)ethane according to the procedure as described in Example 16.53 and the indifference was applied to afford 442-(2- Methoxyethoxy)ethoxymethyl-2,3_dihydrospiro[furo[2,3-g][l,4]benzodioxolene_8,3·-吲哚-2,(1Ή)-one (26%), as a colorless solid: m.p.: 109-110 ° C; iHNMR pOOMHz 'DMSOO δ 7.30 (dd, J = 8.1, 8.1 Hz, 1H), 6.73 (dd, J = 8.1 , 5.6 Hz, 1H), 6.39 (s, 1H), 6.12 (s, 1H), φ 4.69 (ABq, 2H), 4.17-4.07 (m, 4H), 4.01-3.91 (m, 2H), 3.49 (t , J = 4.5 Hz, 2H), 3.38-3.31 (m, 4H), 3.20 (s, 3H), 3.15 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.0, 155.1, 154.3, 144.4 , 143.6, 137.0, 130.1, 120.0, 116.7, 110.7, 107.4, 102.1, 98.0, 76.5, 71.2, 69.7, 68.7, 68.0, 64.1, 63.5, 57.9, 56.5, 26.5 ; MS (ES+) m/z 428.1 (M + 1). Example 16.55 l'_Methyl-4'-{[3-(Trifluoromethyl)p-pyridinyl-2-yloxy) 2,3-dihydrospiro[吱,[2,3-g] [l,4]benzodioxanthene-8,3'_蚓哚]_2, (1, synthesis of ketone- ketone 143924-sp-20091127-6 •905- 201020257

Following the procedure as described in Example 16.53, and performing an insignificant change, 2-bromo-3-(trifluoromethyl) &gt; 2-bromopyridine was substituted with pyridine to give the oxime-methyl-4'- {[3-(Trifluoromethyl)acridin-2-yl]oxybu 2,3-dihydrospiro[olleno[2,3-g][l,4] benzodioxanthene -8,3^引哚]-2'(1Ή)-ketone (44%), as colorless solid: melting point &gt;250°C; 1H NMR (300 MHz, DMSO-d6) 5 8.11-8.06 (m, 2Η ), 7.42 (dd, J = 8.0, 8.0 Hz, 1H), 7.17 (dd, J = 7.5, 5.0 Hz, 1H), 7.05 (d, J = 7.8 Hz, 1H), 6.78 (d, J = 8.3 Hz) , 1H), 6.07 (s, 1H), 6.04 (s, 1H), 4.61 (ABq, 2H), 4.11-3.93 (m, 4H), 3.21 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6 ) δ 176.7, 159.0, 155.2, 151.1, 148.7, 145.6, 144.1, 137.8 (10), 137.4, 130.6, 125.0, 123.3, 118.8, 117.9, 112.3, 112.1, 111.6, 107.0, 98.2, 78.1, 64.5, 63.9, 57.0, 27.3 MS(ES+)m/z470.9(M+l) 〇Example 16.56 Γ-Methyl-4·-[4-(Trifluoromethyl)phenoxy]-2,3-dihydrospiro And [2,3_g][14] Synthesis of benzodioxanthene-8,3·-啕哚]-2'(1Ή)-one

Following the procedure as described in Example 16.53 and performing an insignificant change, the 2-bromopyrrole was replaced with 1-bromo-4-(trifluoromethyl)benzene to give the hydrazine methyl 143924-sp-2009U27- 6 -906- 201020257

-4·-[4-(Trifluoromethyl)phenoxy]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 , 3L 吲哚]-2'(1Ή)-one (36%), as colorless solid: mp 198-201 °C; 1H NMR (300 MHz, DMSO-d6) &lt;5 7.52 (d, J = 8.7 Hz , 2H), 7.44 (dd, J = 8.1, 8.1 Hz, 1H), 7.06 (d, J = 7.8 Hz, 1H), 6.74 (dd, J = 8.3, 1.9 Hz, 3H), 6.19 (s, 1H) , 6.10 (s, 1H), 4.66 (ABq, 2H), 4.12-3.93 (m, 4H), 3.23 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 176.2, 154.6, 149.8, 145.1, 143.8, 137.2, 130.6, 126.6 (m), 123.1, 122.8, 122.4, 118.8, 116.2, 115.4, 111.1, 106.2, 98.0, 77.6, 64.0, 63.3, 56.4, 26.8; MS (ES+) m/z 470.1 (M + 1). Example 16.57 4'-(Benzyloxy)-indole-methyl-2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxanthene-8,3 '-哚哚]-2'(1Ή)-ketone synthesis

At ambient temperature, 4·-hydroxy-1,-fluorenyl-2,3_dihydrospiro[bite and [2,3-g][l,4] bis-lactene-8, 3% 嗓]]-2'(1Ή)-ketone (0.25 g, 0.77 mmol), benzyl bromide (0.13 mL, 1.1 mmol), and cesium carbonate (0.751 g, 2.30 mmol) They were combined in anhydrous hydrazine, hydrazine-dimethyl guanamine (ml) and stirred for 16 hours. The reaction mixture was concentrated in vacuo and EtOAcqqqqqqqqq The organic layer was dehydrated and dried with sulfuric acid, filtered and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate in 二% to 1% by weight gradient in di-methane, followed by recrystallization from methanol/second gas, to give 4,_ Methyl-2,3-dihydrospiro[[,,,,,,,,,,,,, -2'(1Ή)-ketone (0.130 g, 41%) as colorless solid: mp 198-200 ° C; lH NMR (300 MHz, DMSO-d6) δ 7.32-7.23 (m, 4H), 7.03 7.01 (m, 2H), 6.81 (d, J = 8.5 Hz, 1H) 6.74 (d, J = 7.8 Hz, 1H), 6.44 (s, 1H), 6.20 (s, 1H), 5.06 (s, 2H) , 4.70 (ABq, 2H), 4.19-4.11 (m, 4H), 3.16 (s, 3H) ; 13 C NMR (75 MHz, DMSO-d6) δ 177.4, 155.8, 154.4, 145.0, 144.3, 137.8, 137.3, 130.6, 128.5, 127.9, 127.0, 120.5, 117.6, 111.5, 108.1, 102.8, 98.8, 77.5, 69.1, 64.7, 64.1, 57.7, 27.1; MS (ES+) m/z 416.0 (M + 1) « Example 16.58 Γ- Mercapto-4'-{[3-(trifluoromethyl&gt;pyridin-2-yl)methoxy}-2,3-dihydrospiro [bito-[2,3-g][l, 4] Synthesis of benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one

Purification of the ruthenium bromide using 2-(azepine fluorenyl)-3-(trifluoromethyl)-pyridine hydrochloride to obtain a ruthenium-fluorenyl group according to the procedure as described in Example 16.57, and subject to insignificant changes. -4'-{[3-(Trifluoromethyl)pyridin-2-yl]decyloxy 2,3-dihydrospiro[N-[2,3-g][l,4]benzoic Oxadecene-8,3'-indole]-2'(1Ή)-one (44%) as a colorless solid: mp 157-159 ° C; iHNMR pOOMHz 'DMSO-A) δ 8.77 (d, J = 4.7 Hz, 1H), 8.17 (d, J = 7.9 Hz, 1H), 7.61 (dd, J = 8.0, 4.9 Hz, 1H), 7.31 (dd, J = 8.1, 8.1 Hz, 1H), 6.83 (d, J = 8.5 Hz, 1H), 6.75 (d, J = 7.8 Hz, 1H), 6.06 (s, 1H), 6.01 (s, 1H), 5.16 (ABq, 2H), 4.59 (ABq, 2H), 4.14- </ RTI> <RTIgt; , 122.2, 120.1, 143924-sp-20091127-6 -908- 201020257 117.6, 111.2, 107.9, 103.0, 98.0, 77.1, 69.2, 64.6, 64.0, 57.0, 27.1; MS (ES+) m/z 484.8 (Μ + 1 ). Example 16.59 446-(Dimethylamino)pyridin-3-yl)-1·-(acridin-2-ylindenyl)-3,7-dihydro-2H-spiro[benzofuran[5,6 -b] Synthesis of [l,4]dioxolene _8,3,_dihydrocrylate]-2,-one

The porphyrin-3-3-dihydroxyborane was replaced with 2-(dimethylamino)pyridine-5-dihydroxyborane according to the procedure as described in Example 2.46, and the change was inconsequential, and 4' was used. -bromo-indenyl-(pyridin-2-ylindenyl)-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxene-8,3' -吲哚]-2'(1|11)-keto-substituted 4|-bromo-indole-(diphenylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l , 4] benzodioxanthene-8,3. 5丨哚]-2'(1Ή)-one, obtaining 4·-(6-(dimethylamino)p-pyridin-3-yl)- Γ-〇 啶 〇 〇 〇 〇 〇 〇 〇 [ [ 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 笨 [5,6-b][l, '-Dihydroanthracene-2'-one (44%), colorless solid: mp 187-188T: (methanol / di-methane); 4 NMR (300MHz, CDC13) 5 8.61-8.56 (m,lH), 7.80-7.77(m, 1H), 7.70-7.62 (m, 1H), 7.32-7.17 (m, 3H), 6.91-6.81 (m, 2H), 6.66 (dd, J = 8.8, 2.5 Hz, 1H), 6.40 (s, 1H), 6.27 (s, 1H), 6.21 (d, J = 8.8 Hz, 1H), 5.25 (d, J = 15.8 Hz, 1H), 4.93 (d, J = 15.8 Hz, 1H), 4.71 (d, J = 9.0 Hz, 1H), 4.46 (d, J = 9.0 Hz, 1H), 4.30-4.08 (m, 4H), 3.05 (s, 6H); 13 C NMR (75 MHz, CDC13) δ 178.2, 158.5, 155.6, 155.4, 149.5, 147.4, 144.7, 142.7, 138.0, 137.6, 137.2, 143924-sp-20091127-6 • 909-201020257 137.1, 129.5, 128.8, 125.9, 122.8, 122.7, 122.0, 121.7, 111.2, 108.6, 104.3, 99.4, 64·6, 64·0, 58.4, 46.2, 38.1; MS (ES+) m/z 507.0 (M + l). Example 16.60 4'-(4-Indolylphenyl)-indole-indole-pyridin-2-ylindenyl)-3,7-dihydro-2H-spiro[benzofuro[5,6-b] Synthesis of [l,4]dioxane sulphate-8,3'-dihydroindole]-2·-one

Following the procedure as described in Example 2.46, and carrying out irrelevant changes, quinolin-3-yldihydroxyborane was replaced with 4-methoxyphenyldihydroxyborane and 4'-bromo-indole was used. (pyridin-2-ylmethyl)-2,3-dihydrospiro [bito-[2,3-g][l,4]benzodioxolene-8,3^5丨哚]- 2'(1Ή)- Stirring 1 replacement anal bromide-Γ-(diphenylhydrazinyl)-2,3-dihydrospiro [bito-and-[2,3$][1,4]benzodioxan Alkenyl-8,3'-indole]-2'(1 ugly)-ketone 'obtains 4'-(4-indolylphenyl)-indole-(pyridin-2-ylmethyl)-3,7-di Hydrogen-2Η-spiro[benzofuro[5,6-b][l,4]dioxolene-8,3'-diindol]-21-one (68%) as a colorless solid : melting point 205-206 ° C (ethyl acetate / hexane); 1 H NMR (300 MHz, CDC 13) (5 8.59 (d, J = 4.7 Hz, 1H), 7.65-7.68 (m, 1H), 7.32- 7.17 (m, 3H), 6.91-6.84 (m, 2H), 6.78-6.61 (m, 4H), 6.41 (s, 1H), 6.25 (s, 1H), 5.26 (d, J = 15.8 Hz, 1H) , 4.92 (d, J = 15.8 Hz, 1H), 4.68 (d, J = 9.0 Hz, 1H), 4.36 (d, J = 9.0 Hz, 1H), 4.27-4.08 (m, 4H), 3.77 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 178.3, 158.9, 155.6, 155.5, 149.5, 144.6, 142.6, 140.0, 137. 9,137.1,130.9, 129.8, 129.0, 128.7, 125.7, 122.9, 122.8, 121.7, 113.2, 111.1, 108.5, 99.4, 143924-sp-20091127-6 -910- 201020257 64.6, 64.0, 58.5, 55.3, 46.2 ; MS (ES+ m/z 493.0 (Μ + 1). Example 16.61 (7S)-4'-Eryt-3-yl-indole-indenyl snail [吱 并和阳 (3) benzodioxolan-7,3 '-啕哚]_2|(1汜)-ketone synthesis

4 4'-furanyl--1,-methylspiro[吱,[2,3-f][l,3]benzodioxene-7,3'-吲哚]-2' (1Ή)-ketone (950 mg, 2.63 mmol) was resolved on a semi-preparative palmitic beta column (CHIRALPAK-IA 'Plant Technology) with 2% acetonitrile in a third-butyl methyl ether. Dissolved at 30 ml/min (25 min operating time). Each operation contained 50 mg of the racemate dissolved in acetonitrile / tert-butyl-f-ether (1:1). (7S&gt;4,_furan_3_yl_Γ_曱yl snail [furan [2,3- phantom [1,3] benzooxy oxene _7,3'-»»5 卜] _2|(1'11)-ketone is the first dissolved isomer of the palm. Recrystallized from di-halogenane and diethyl ether to obtain (7S)_4,_吱pyr Φ winter base-1'-methyl snail [furo[2,3-f][l,3]benzodioxolene _7,3··吲

11 ]]-2'(1Ή)-ketone (0.38 g, 79%), colorless solid: melting point i44-145°C (2 gas smoldering / screaming wide 1!! NMR (300 MHz, CDC13) &lt;;5 7.38-7.30 (m, 2H), 7.00 (dd, J = 7.9, 0.9 Hz, 1H), 6.89-6.81 (m, 1H), 6.42 (s, 1H), 6.21 (s, 1H), 6.05- 6.03 (m, 1H), 5.89 (d, J = 1.3 Hz, 1H), 5.85 (d, J = 1.3 Hz, 1H), 4.72 (d, J = 9.1 Hz, 1H), 4.57 (d, J = 9.1 Hz, 1H), 3.27 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.1, 156.2, 149.1, 144.2, 142.8, 142.0, 140.4, 131.0, 129.1, 128.2, 125.4, 122.5, 120.8, 111.1, 107.5 , 102.8, 101.6, 93.9, 58.5, 26.9; MS 143924-sp-20091127-6 -911 · 201020257 (ES+) m/z 361.9 (Μ + 1). (7RH,-吱吱钱七分子螺(四)# [ 2, which view and: oxygen Wuyuan thin -7 '3 '1 哚] -2, (1 Ή) - ketone synthesis

4'-Indolyl-3-yl-1,-indoleyl snail [biting sulphide [2,3.,3] benzodioxolan -7-3,-&lt;哚]-2, ( 1Ή&gt; Ketone (950 mg, 2.63 mmol) was resolved on a semi-preparative palmitic column (CHIRALPAK-IA 'Plant Technology Co., Ltd.) and 2% acetonitrile in the third butyl methyl hydrazine. Dissolved at 3 G ml/min (25 min operating time). Each run contained 50 mg of the racemate dissolved in acetonitrile/t-butylmethyl bond (ι:ι). (7R)_4'_furan_3 _基_Γmethyl snail [biting and [2'3-f][l,3]benzodioxene _7,3,_吲哚]_2Ι(1Ή) ketone is the second solvate The palm isomer is recrystallized from dioxane and diethyl ether to obtain (7R) 4, furan-3-yl-indole-fluorenyl [pyrano[2,3-^,3]benzodioxole圜 圜 _ 7 7 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 300 MHz, CDC13) 5 7.38-7.30 (m, 2H), 7.00 (dd, J = 7.9, 0.6 Hz, 1H), 6.89-6.81 (m, 1H), 6.42 (s, 1H), 6.21 (s, 1H) ), 6.05-6.03 (m, 1H), 5.89 (d, J = 1.2 Hz, 1H), 5.85 (d, J = 1.2 Hz, 1H), 4.72 (d, J = 9.1 Hz, 1H), 4.57 (d, J = 9.1 Hz, 1H), 3.27 (s, 3H) ; 13 C NMR (75 MHz,

CDC13) δ 178.1, 156.2, 149.1, 144.2, 142.8, 142.0, 140.4, 131.0, 129.1, 128.2, 125.4, 122.5, 120.8, 111.1, 107.5, 102.8, 101.6, 93.9, 58.5, 26.9; MS 143924-sp-20091127- 6 -912· 201020257 (ES+) m/z 361.9 (Μ + 1). Example 16.63 (7R)-4'_Momot-1'-methylspiro[吱,[2,3na,3] stupid and dioxocene]_3 3,·1丨哚]-2' ( 1Ή)-ketone synthesis

4·-Bromo-indenyl-methylspiro[吱-benzobenzodioxene_7,3,_® 啕哚]-2'(1Ή)-one (0.32 g, 8.58 mmol) Analyzed on a semi-preparative palmitic column (CHIRALPAK-IA 'Plant Technology Co., Ltd.), dissolved in 5% acetonitrile in a third butyl methyl ether at 30 ml/min, each solution containing dissolved 5 mg of the racemate in acetonitrile / tri-butyl methyl ether (1:1). (7R)-4-bromo-1-methyl snail [bito-and-[2,3-f][l,3]benzodioxanthene _7 3,_ 11 wood]-2 (1 H The ketone (0.14 g, 86%) is the first dissolving palmomer, and is obtained as a crystalline colorless solid: mp 226-228. (:(acetonitrile/tertiary-butyl methyl ether); if! NMR (300 MHz, DMSO-d6) (5 7.31-7.23 (m, 1H), Ref. 7.20-7.15 (m, 1H), 7.12-7.08 (m , 1H), 6.59 (s, 1H), 6.28 (s, 1H), 5.92-5.87 (m, 2H), 4.82 (d, J = 9.7 Hz, 1H), 4.67 (d, J = 9.7 Hz, 1H) , 3.15 (s, 3H) ; MS (ES+) m/z 373.8, 375.8 (M + 1). Example 16.64 (7S)-4'_Momot-Γ-methyl snail [吱α南和[2,3_f Synthesis of [i,3]benzodioxanthene _7,3 "bow 丨哚]-2'(1Ή)-ketone 143924-SP-20091127-6 -913- 201020257

4'-Bromo-indenyl-fluorenyl snail [bito-[2,3-f][l,3]benzodioxene _7 3,_ 吲哚]-2·(1Ή)- The ketone (0.32 g, 8.58 mmol) was resolved on a semi-preparative palmitic column (CHIRALPAK-IA, for the palm technology company) and in 5% acetonitrile in the third-butyl decyl ether. Dissolved at 30 ml/min, each operation containing 50 mg of the racemate dissolved in acetonitrile / tert-butyl decyl ether (1:1). (7S)~4'-Moji-Γ-Methyl snail 〇 并 [2,3-f][l,3]benzodioxanthene ❹ 丨嗓]-2'(1Ή)-ketone (0.13 g, 81%) is the second dissolving of the palmomer isomer' and is isolated as a crystalline colorless solid: melting point 226-227 ° C, (acetonitrile / tert-butyl methyl ether); 1 η NMR (300 MHz, DMSO-d^) 5 7.31-7.23 (m,1H) 7.20-7.15 (m, 1H), 7.12-7.08 (m, 1H), 6.59 (s, 1H), 6.28 (s, 1H), 5.92- 5.87 (m, 2H), 4.82 (ds J = 9.7 Hz, 1H), 4.67 (d, J = 9.7 Hz, 1H), 3.15 (s, 3H) ; MS (ES+) m/z 373.8, 375.8 (M + 1) 〇 Example 16.65 (7S)-4'_吱 Drink-3-yl snail [吱, [[2,3. 3] benzodioxolane _7,3,_w ❿ 哚]-2\1Ή )-ketone synthesis

Make 4'-snack -3-yl snail [cough and [2,3,3] benzodioxolane _7,3,_ρ丨嗦丨嗦]-2'(1Ή)-嗣(0.25克) Analyzed on a semi-preparative palmitic column (CHIRALpAKIA, for palm technology company) and in 5% ethyl 143924-sp-20091127-6 • 914- 201020257 nitrile in the third butyl methyl ether, at 30 Dissolved in cc/min, each operation consisting of a 50 mg excipient which was first dissolved in dimethyl amide (0.15 ml) and diluted with acetonitrile (〇·85 ml) and tri-butyl methyl ether (1.00 ml). Swirling. The product was dissolved in dimethyl sulphate (2.0 ml), precipitated with water (50.0 ml), filtered, and air dried to give (7S)_4'-furan-3-yl snail [biting and sing [2, 3-f][l,3]benzodioxanthene _7,3,_, 丨哚 丨哚]-2'(1Ή)-one (0.11 g, 88%), as a colorless solid. This pair of palm isomers is the first eliminator. Melting point 230-231°C OM^HNMRGOOMHzJMSO-d6) δ 10.64 (s, 1Η), 7.57 (dd, J = 1.6, 1.6 Hz, 1H), 7.27 (dd, J = 7.8, 7.8 Hz, • 1H), 7.03 (s, 1H), 6.90 (dd, J = 7.1, 7.1 Hz, 2H), 6.55 (s, 1H), 6.32 (s, 1H), 6.06 (d, J = 0.8 Hz, 1H), 5.92 (d , J = 4.8 Hz, 2H), 4.60 (d, J = 9.4 Hz, 1H), 4.44 (d, J = 9.4 Hz, 1H); 13C NMR (75 MHz, DMSO-d6) 5 179.2, 156.1, 148.8, 143.8, 143.3, 142.0, 140.5, 130.5, 129.6, 128.9, 124.3, 123.2, 121.4, 111.3, 109.7, 103.3, 101.9, 93.7, 77.6, 58.6; MS (ES+) m/z 347.9 (M + l). Example 16.66 (7R)-4,-furan-3-yl snail [c-buto[2,3-f][l,3]benzodioxolene _7,3|_啕哚]-2' (ΓΗ)-ketone synthesis

4'-furan-3-yl spiro[吱然[[Hungry benzodioxanthene_7,3·_ρ5丨嗓]-2'(1Ή)-one (0.25 g) in semi-preparative Analyze the palmar column (CfflRALpAKIA, for the palm technology company) and dissolve it in 30 ml/min with 5% acetonitrile in the third-butyl methyl ether. Each operation contains the first dissolved in two \ 143924 -sp-20091127-6 • 915- 201020257 50 mg of the racemate diluted in acetonitrile (0.15 ml) with acetonitrile (0.85 ml) and a tri-butylmethyl bond (1.00 ml). The isolated product was dissolved in dimethyl hydrazine (2.0 ml), precipitated with water (50.0 ml), filtered, and air dried to give (7R)-4'-furan-3-yl snail And [2,3-f][l,3]benzodioxanthene-7,3'-吲哚]-2f(rH)-one (0.10 g, 75%) was obtained as a colorless solid. The palm isomer is the second eliminator: melting point 229-231 ° C (water); iH NMROOO MHz, DMSO-dg) δ 10.64 (s, 1H), 7.57 (dd, J = 1.6, 1.6 Hz, 1H) , 7.27 (dd, J = 7.8, 7.8 Hz, 1H), 7.03 (s, 1H), 6.90 (dd, J = 7.1, 7.1 Hz, 2H), 6.55 (s, 1H), 6.32 (s, 1H), 6.06 (d, J = 0.8 Hz, 1H), 5.92 (d, J = 4.8 Hz, 2H), 4.60 (d, J = 9.4 Hz, 1H), 4.44 (d, J = 9.4 Hz, 1H) ; 13C NMR (75 MHz, DMSO-d6) δ 179.2, 156.1, 148.8, 143.8, 143.3, 142.0, 140.5, 130.5, 129.6, 128.9, 124.3, 123.2, 121.4, 111.3, 109.7, 103.3, 101.9, 93.7, 77.6, 58.6; (ES+) m/z 347.9 (M + l). Example 16.67 1'-Methyl-4'-(lH-pyrazol-3-yl)-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxan Synthesis of terpene-8,3'-嘀哚]-2'(ΓΗ)-ketone

According to the procedure as described in Example 2.46, and irrelevant changes were made, porphyrin-3-yldihydroxyborane was replaced with 1 -pyrazol-3-dihydroxyborane, and bromine-purine-methyl was used. Base snail [Miso-[2,3-f][i,3]benzodioxene _7,3,_Ρ?丨哚]-ΜΗ)-one substituted 4,-bromo-1,- (diphenyl fluorenyl) 2,3_dihydrospiro[味喃和143924-sp.20091127-6 -916· 201020257 [2,3-g][l,4]benzodioxanthene-8 , 3'-峋哚]_2, (1Ή)-ketone, obtained Γ-mercapto-4'-(1Η-ρ ratio)--3-yl)-2,3-dihydrospiro[吱喃和[2 ,3-g][l,4]benzodioxanthene-8,3'-峋哚]-2'(1Ή)-one (63%), colorless solid: melting point 2〇i_2〇2° C (di-methane/diethyl ether); 4 NMR (300 MHZ, CDC13) &lt;5 7.46-7.35 (m, 2H), 7.25-7.20 (m, 1H), 6.92 (d, J = 7.7 Hz, 1H), 6.40 (s, 1H), 6.24 (s, 1H), 5.94 (d, J = 2.0 Hz, 1H), 4.74-4.61 (m, 2H), 4.20-4.07 (m, 4H), 3.27 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 178.0, 155.6, 144.7, 144.5, 137.8, 129.2, 128.0,

124.6, 121.6, 111.0, 108.2, 105.5, 99.5, 77.4, 64.5, 63.9, 58.4, 26.9; MS © (ES+) m/z 375.9 (M + 1). Example 16, 68 4'-吱"South-3-yl-indole-methyl-2,3-dihydrospiro[吱,[2,3_§][1,4]benzodioxanthene- Synthesis of 8,3·-吲哚]-2,(1Ή)-ketone

_ follow the procedure as described in Example 2.46, and perform an insignificant change' using 3-p-fusin-based singularity to replace u-quinone-3-yldi-based boron-based, and use 4'-bromo -Γ-曱基螺[吱,[2,3-f][l,3]benzodioxolene-7,3,-峋哚]-2'(1Ή)-ketone replacement 4'- Bromo group_ι,_(diphenylmethyl)_2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3·_,哚]_2,(1Ή),, obtain 4ι_咬咬_3_ Γ-Γ-mercapto-2,3-dihydrospiro[吱,[2,3_g][i,4]benzodioxanthene _8,3,-吲嗓]-2'(1Ή)-ketone (65%) as colorless solid: mp 178_18 〇 «c (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) 5 7.38 -7.29 (m, 2H), 7.00 (d, J = 7.9 143924-sp-20091127-6 -917- 201020257

Hz, 1H), 6.86 (d, J = 7.8 Hz, 1H), 6.76 (s, 1H), 6.41 (s, 1H), 6.28 (s, 1H), 6.04-6.01 (m, 1H), 4.68 (d , J = 9.0 Hz, 1H), 4.53 (d, J = 9.0 Hz, 1H), 4.23-4.09 (m, 4H), 3.26 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 155.5, 144.7, 144.3, 142.8, 140.5, 137.9, 130.8, 129.1, 128.1, 125.2, 122.6, 122.5, 111.2, 111.1, 107.4, 99.7, 76.7, 64.6, 64.0, 58.3, 26.8; MS (ES+) m/z 375.9 (M +l). Example 16.69 Γ-Mercapto-4H1H-pyrazol-4-yl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8, Synthesis of 3'-吲哚]-2'(1Ή)-ketone

Following the procedure as described in Example 2.46, and performing an insignificant change, replacing the quinoline-3-yldihydroxyborane with 1?-pyrazole-4-dihydroxyborane and using 4'-bromo-indole -Methylspiro[吱,[2,3-f][l,3]benzodioxanthene-7,3,-吲哚]-2'(1Ή)-one substituted 4'-bromo -Γ-(diphenylfluorenyl)_2,3_dihydrospiro [snolo[2,3$][1,4]benzodioxolene-8,3'-峋哚]-2 '(1'11)-ketone, which gives 1,-mercapto-4Η1Η-pyrazol-4-yl)-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzene Dioxetene-8,3'-anthracene-2·(1Ή)-one (54%) is a colorless solid: m.p. 250-251. (: (ethyl acetate / hexane); 1H NMR (300 MHz, CDC13) 5 7.35 (dd, J = 7.9, 7.9 Hz, 1H), 7.10-7.00 (m, 3H), 6.86 (d, J = 7.8 Hz, 1H), 6.40 (s, 1H), 6.31 (s, 1H), 4.66 (d, J = 9.1 Hz, 1H), 4.47 (d, J = 9.1 Hz, 1H), 4.23-4.08 (m, 4H ), 3.26 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 155.4, 144.8, 144.3, 138.0, 143924-sp-20091127-6 _918„ (S) 201020257 130.6, 129.2, 127.9, 125.4, 122.5 , 111.4, 107.3, 99.6, 64.6, 63.9, 58.2, 26.8; MS (ES+) m/z 376.0 (Μ + 1) 〇 Example 16.70 1·-Methyl-4H1-methyl-lH-p ratio e--4 -yl)-2,3-dihydrospiro[pfrano[2,3_g][i,4]benzodioxanthene-8,3'-岣哚]-2'(1Ή)-one Synthesis

Using 1-methyl-4-(4,4,5,5-tetradecyl-1,3,2-dioxy-deuterium-in accordance with the procedure described in Example 2.46 and performing an insignificant change 2-yl)-1Η-ρ is 0-substituted quinolin-3-yldihydroxyborane and uses 4'-bromo-indenyl-methyl snail [吱,[2,3&lt;|[1,3 Benzodioxanthene-7,3'-throindole]-2'(1)-ketone replacement 4|-bromo-1'-(diphenylmethyl)-2,3-dihydrospiro [吱吱[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one, obtaining 1·-methyl-4' -(l-methyl-1H-pyrazol-4-yl)-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8, 3'-吲哚]-2'(1Ή)-ketooxime (58%) as colorless solid: m.p. 220-222°C (ethyl acetate/hexane); WNMR

(300 MHz, CDC13) δ 7.32 (dd, J = 7.9, 7.9 Hz, 1H), 7.16 (s, 1H), 6.99 (d, J = 7.8 Hz, 1H), 6.83 (d, J = 7.8 Hz, 1H ), 6.53 (s, 1H), 6.42 (s, 1H), 6.31 (s, 1H), 4.66 (d, J = 9.1 Hz, 1H), 4.48 (d, J = 9.1 Hz, 1H), 4.23-4.09 (m, 4H), 3.75 (s, 3H), 3.25 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.0, 155.6, 144.8, 144.2, 138.7, 138.0, 130.8, 129.3, 129.1, 127.8, 125.2 , 122.7, 119.0, 111.5, 107.0, 99.4, 76.7, 64.6, 64.0, 58.3, 38.9, 26.8; MS (ES+) m/z 390.0 (M + 1). 143924-sp-20091127-6 •919- 201020257 Example 16.71 Γ-Methyl-2'-keto-l',2,2',3-tetra-argon snail [吱,[2,3-g][l , 4] Synthesis of benzodioxolene-8, 吲哚]-4'-carbonitrile

Following the procedure as described in Example 2.48, and applying an insignificant change, 4'-bromo-indenyl-methylspiro[吱,[2,3-f][l,3]benzodioxene was used. Terpene-7,3,-qiao嗓]-2'(1Ή)-嗣substituted 6-bromo-indenyl-(diphenylmethyl)spiro[1_benzofuran-3,3,-啕鲁啕] -2'(1Ή)-嗣' obtained Γ-mercapto-2, keto group_ι,, 2,2,,3-tetrahydrospiro[吱,[2,3-g][l,4] Benzodioxanthene _8,3'-indole]-4,-carbonitrile (74%) as colorless solid: mp 196-197 ° C (ethyl acetate / hexane); 1 NMR 300 MHz, CDC13) δ 7.47-7.36 (m, 1Η), 7.32-7.27 (m, 1H), 7.11-7.07 (m, 1H), 6.52 (s, 1H), 6.14 (s, 1H), 4.94-4.83 (m, 2H), 4.22-4.06 (m, 4H), 3.28 (s, 3H); MS (ES+) m/z 334.9 (M + 1). Example 16.72 Γ-Mercapto-2'-keto-l',2,2',3-tetrahydrospiro[吱,[2,3_g][1,4]benzodioxanthene

Dilute _8,3%5丨哚]_4ι_Synthesis of decylamine η2ν λ — Γ-mercapto-2'-keto-1',2,2',3-tetrahydrospiro 2,3_g][14] benzodioxanthene-8,3'-啕哚]-4'-carbonitrile (〇25g, 〇75mmol) in ethanol (9) ml) A saturated aqueous solution of sodium carbonate (3 ml) and 3 〇 143924-sp-20091127-6-920- 201020257 % w/w aqueous hydrogen peroxide (3 ml) were added. The reaction mixture was heated at reflux for 3 h, cooled to rt and concentrated in vacuo. The residue was triturated in water to give hydrazine-methyl-2'-keto-^-^-tetrahydrospich-[2,3-g][l,4]benzodioxanthene -8,3'-吲哚]-4'-carboxamide (0.09 g, 33%), as colorless solid: melting point &gt; 250 ° C (water); 1H NMR (300 MHz, CDC13) δ 7.59 (s , 1Η), 7.43-7.36 (m, 1H), 7.24-7.13 (m, 3H), 6.28 (s, 1H), 5.98 (s, 1H), 5.15 (d, J = 8.1 Hz, 1H), 4.57 ( d, J = 8.1 Hz, 1H), 4.16-3.99 (m, 4H), 3.13 (s, 3H); MS (ES+) m/z 352.9 (M + 1). Example 16.73 1'-Methyl 1(tetrahydrofuran-3-yl)spiro[吱,[2,3-f][l,3]benzodioxol-7,3W丨哚]-2' ( 1Ή)-ketone synthesis

4'-Furan-3-yl-indole-methyl snail [Mun-[2,3-f][l,3]benzodioxanthene φ -7'3, 丨哚]-2 '(1'11)-_(〇.60g '1.66 mmol) in a solution of ethyl acetate (3 mL), palladium/carbon (10% w/w, 〇.4 gram) . The reaction mixture was shaken under hydrogen pressure (60 psi) in a Parr hydrogenation apparatus at ambient temperature for 16 hours and filtered through a pad of Celite. The filtrate was concentrated in vacuo, and the residue was crystallised from methylene chloride / diethyl ether to afford </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; </RTI> <RTIgt; 3] benzodioxanthene _7,3,_吲哚]-2'(ΓΗ)-one (0.44 g, 73%), as a colorless solid: mp 182 184 s (m. ,1H NMR (300 MHz, CDC13) δ 7.31-7.35 (m, 1H), 7.08-7.01 (m, 1H), 143924-sp-20091127-6 •921 - 201020257 6.77 (d, J = 7.7 Hz, 1H) , 6.52-6.48 (m, 1H), 6.15 (d, J = 13.3 Hz, 1H) 5.90-5.84 (m, 2H), 4.96 (dd, J = 9.26, 1.0 Hz, 1H), 4.78-4.67 (m&gt; 1H) 4.11-3.59 (m, 3H), 3.39-3.18 (m, 2H), 2.40-1.94 (m, 1H), 1.63-1.36 (m 1H) ; MS (ES+) m/z 365·9 (M + 1). Example 16.74 1·-Methyl-4·-(5-methyl-1,2,4-oxadiazoleyl)-2,3-dihydrospiro[Homo-[2,3-g][l ,4] Synthesis of benzodioxanthene-8,3'-啕哚]-2·(1Ή)-one

Γ-曱-yl-2'-keto-oxime, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8, 3'-Chaoyu]-4'-phthalonitrile (0.35 g, 1.05 mmol) in a solution of diterpenoid (1 mL) Adding hydroxylamine (50% w/w solution in water, 3 .〇ml). The reaction mixture was stirred at ambient temperature for 16 h then poured over EtOAc EtOAc. The combined organic extracts were washed with brine (2x 50 mL) The residue was triturated in hexane to give N,-hydroxyindol-2'-keto-3,7-dihydro-2H-spiro[benzofuro[5,6-b][l,4 Dioxane sulphate-8,3'-dihydroindole]-4'- succinimide amide (〇.37 g) is a colorless solid. In a 10 ml microwave reaction vessel, N,_hydroxy-Γ-曱-yl 2,-keto- 3,7-dihydro-2-indole-spiro[benzopheno[5,6-7]-like Oxalene-8,3,dihydrotetramine]_4,_carbolineimine decylamine (0.20 g, 〇.54 mmol), acetic anhydride (〇 5 mL) and pyridine (2.00 mL). The solution was heated in a microwave reactor at 16 Torr. 5 small 143924-sp-20091127-6 201020257

It was allowed to cool to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography eluting with hexane / ethyl acetate (3/1), and then recrystallised from diethyl ether to give s-methyl- 4,-(5-methyl-1,2 , 4-oxadiazol-3-yl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3'_吲嗓]_2·(ιή)-remaining (〇.〇8 g '37%) as a colorless solid: melting point i99_2〇rc (diethyl ether); 1 η NMR (300 ΜΗζ, CDC13) δ 7.70 (dd, J = 8.0, 0.8 Hz, 1H), 7.46 (t, J = 7.9 Hz, 1H), 7.03 (dd, J m/z 391.9 (M + 1). =7.8, 0.8 Hz, 1H), 6.39 (s, 1H), 6.03 ( s, 1H), 5.14 (d, J = 8.6 Hz, 1H), 4.82 (d, J = 8.6 Hz, 1H), 4.16-4.00 (m, 4H), 3.28 (s, 3H), 2.50 (s, 3H MS (ES+) Example 16.75 4|-(3,5-Dimercaptoisoxazole)-r_indolyl 2,3_dihydrospiro [Blowing and [2,3-g][l , 4] The synthesis of bis, dioxin, dioxin, _8, 3'_4, and _2'(i'h) ketone

' 'Add 4'-bromo-indenyl-methyl snail in a W ml reaction vessel [吱〇南和[2,3-幻[1,3]benzodioxene-7,3,-ten ]]-2Χ1Ή)-ketone (0.50 g, 1,3 mmol), 3,5-dimercaptoisoxazole-4-dihydroxyborane (0.37 g, 2 6 mmol), palladium acetate ( 0.018 g, 0.026 mmol, dicyclohexylphosphino-2,6-dimethoxybiphenyl (0.021 g, 0.052 mmol), carbonic acid unloading (〇54 g, 3.9 mmol), Acetonitrile (2.0 ml) and water (1.5 ml). The vessel was heated under microwave irradiation for 1 hr. &lt;&gt;&gt;&lt;&gt;&gt;c, cooled to ambient temperature, diluted with water (25 mL) and extracted with ethyl acetate (3 X 75 mL). The combined organic extracts were washed with brine (5 s s s s sssssssssssssssssssssssssssssssssssssssss The residue was purified by column chromatography and dissolved in a 2% to 60% gradient of ethyl acetate in hexane to give 4,-(3,5-dimercaptoisoxazole)&gt; Γ_曱基-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene_8,3,_吲嗓]-2'(1Ή)- Ketone (0.422 g '80%) 'as colorless solid: mp 228-23 CTC (ethyl acetate/hexane); 1H NMR (mixture of non-neutral isomers, 3 〇〇ΜΗζ, CDC13) δ 7.39-7.29 ( m, 1H), 6.95 (d, J = 7.79 Hz, 1H), 6.73 (d, J = 7.76 Hz, 1H), 6.26 (s, 1H), 6.21 (d, J = 7.14 Hz, 1H), 4.70 ( Dd, J = 8.9, 3.4 Hz, 1H), 4.39 (dd, J = 17.4, 9.0 Hz, 1H), 4.17-4.03 (m, 4H), 3.31 (s, 1.5H), 3.30 (s, ® 1.5H ), 2.24 (s, 1.5H), 2.07 (s, 1.5H), 1.40 (s, 1.5H), 1.32 (s, 1.5H); MS (ES+) m/z 405.0 (M + 1). Example 16.76 Ν,Γ-dimethyl-2'-keto-oxime, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene- Synthesis of 8,3'-p5丨嗓]-4'-treazone

Γ-Mercapto-2'-keto-oxime, 2,2',3-tetrahydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3 '- 丨嗓 丨嗓 -4 -4 - 4 · - oleic acid benzene vinegar (〇. 3 gram, 0.70 millimoles), methylamine hydrochloride (0.12 grams, 1.8 millimoles), potassium carbonate (〇 · 39 grams, 2.8 millimoles) and n,N-dimethylformamide (3.0 ml) were added to the microwave reaction vessel. The reaction was heated in a microwave reactor at 100 C for 5 hours. Further, methylamine salt (0.20 g '3.03⁄4 mol) was added and the mixture was further heated in a microwave reactor at 1 〇〇 143924-sp-20091127-6 • 924-201020257 C for 45 minutes. The mixture was cooled to ambient temperature, poured into water (25 mL) andEtOAc. The combined organic extracts were washed with brine (2x 50 mL The product is precipitated from methylene chloride with diethyl ether and then recrystallized from ethyl acetate to give hydrazine, hydrazine-dimethyl-2, keto-indole, 2,2,,3-tetrahydrospiro[furan [2,3-g][l,4]benzodioxolene _8,3ι_吲哚]4,carboxamide (〇〇8 g '32%), colorless solid: melting point 12〇_ 12Γ(:(ethyl acetate); 1hnmr (300 MHz, CDC13) δ 7.41-7.31 (m, 1H), 7.25-7.19 (m, 1H), 6.98-6.93 (m, ^ 1H)* 6·49 1H) , 6.20 (s, 1H), 5.19 (d, J = 3.2 Hz, 1H), 4.87 (s, 2H), 4.21-4.08 (m, 4H), 3.26 (s, 3H), 2.64 (d, J = 4.9 Hz, 3H) ; MS (ES+) m/z 366·9 (M+ 1). Example 16.77 and Example 16.78 N-cyclobutyl-1 '-indolyl 2i-keto-indole, 2,2,,3_tetrahydrospiro [bito-and-[2,3 g][1,4]benzene And dioxerem-8,3,-吲哚]-4,-carboxamide and hydrazine, hydrazine, hydrazine-trimethyl-2,-keto-1 '2,2''3_tetrahydrogen Snail [biting and [2,3-g][l,4]benzodioxanthene-8,3,-啕哚]-4·-

Γ-Methyl-2'-keto-indole, 2,2',3-tetrahydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3 '-θ丨哚]_4·_D-acid phenyl ester (〇.3〇g, 0.70 mmol), cyclobutylamine hydrochloride (0.23 g, 2.1 mmol), potassium carbonate (0.39 g, 2.8 Millerol) 143924-SO-20091127-6 201020257 and N'N-monodecylguanamine (3 ml) were added to the microwave reaction vessel. The reaction was heated in a microwave reactor at 11 (rc), cooled to ambient temperature, poured into water (25 mL), and extracted with ethyl acetate (3 EtOAc). The organic extract was washed with EtOAc (5 mL) EtOAc (EtOAc)EtOAc. 2% to 100% of the hexane is dissolved in a gradient liquid and then recrystallized from di-methane/diethyl ether to give Ν-cyclobutyl-indole-indolyl-2,-keto-oxime, 2,2, 3-tetrahydrospiro[2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-4,-carboxamide (0.045 g, 17%) ), as colorless solid _ body: melting point 128-129 ° C (diqijiayuan / ether); 4 NMR (300 MHz, CDC13) (5 7.41-7.33 (m, 1H), 7.26-7.21 (m, 1H) , 6.97-6.93 (m, 1H), 6.51 (s, 1H), 6.20 (s, 1H), 5.46 (d, J = 6.65 Hz, 1H), 4.96-4.81 (m, 2H), 4.35-4.01 (m , 5,,,,,,,,,,,,,,,,,, Trimethyl-2,-keto-l',2,2,,3-tetra Snail [吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-4'-carboxamide (0.12 g, 37%) The product is isolated from N-cyclobutyl-fluorenyl-indenyl-2'-keto-l',2,2,3-trihydrospiro[吱,[2,3-g] [1,4] Synthesis of benzodioxanthene-8,3·-,5丨哚]-4'-carboxamide. Obtained as colorless solid stomach: melting point 218-221 ° C (di-methane/diethyl ether); 4 NMR (300 ΜΗζ, CDC13) δ 7.32 (dd, J = 7.8, 7.8 Hz, 1H), 6.91-6.84 (m, 2H), 6.44 (s, 1H), 6.22 (s, 1H), 5.05 (d, J = 8.8 Hz, 1H), 4.79 (d, J = 8.8 Hz, 1H), 4.20-4.04 (m, 4H), 3.28 (s, 3H), 2.79 (s, 3H), 2.19 (s, 3H); MS ( ES+) m/z 381.0 (M + 1). Example 16.79 4'-(3-Methoxyphenoxy)-1'-mercapto-2,3-dihydrospiro[吱,[2,3- Synthesis of phantom [1,4]benzodioxanthene-8,3'-吲哚]-Τ(1Ή)-嗣 143924-sp-20091127-6 -926- 201020257

In a 10 ml sealed tube, packed with 4·-bromo-indole-methyl_3,7-dihydro-2 snail [benzofuro[5,6-b][l,4]dioxan Ace-8,3'-dihydroindole] 2'-one (0.77 g, 2.0 mmol), 3-methoxyphenol (0.50 g '4.0 mmol), potassium carbonate (0.36 g, 2.6 m) Mohr), copper (I) iodide (0.038 g, 0.2 mmol), μMethyl® azole (0.082 g, i.0 mmol) and anhydrous toluene (3 mL). The reaction mixture was heated at 150 ° C for 16 hours' to cool to ambient temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluting with ethyl acetate in 15% to 50% gradient of hexane to give 4-(3-methoxyphenoxy) ))-Γ-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-2' (1Ή)-ketone (0.27 g '31%)' is an off-white solid: mp 166-168 °C (ethyl acetate / hexane); 4 NMR (300 MHz, CDC13) &lt;5 7.20-7.27 (m, 1H ), 7.02-7.10 (m, 1H), 6.68 (d, J = 7.7 Hz, 1H), 6.58 (d, J = 8.4 Hz, 1H), 6.50-6.58 (m, 1H), 6.35-6.29 (m, 1H), 6.25 (s, 1H), 6.21 (t, J = 2.0, Hz, 1H), 6.19 (s, 1H), 4.83 (ABq, 2H), 4.15-4.01 (m, 4H), 3.69 (s, 3H), 3.27 (s, 3H); 13C NMR (75 MHz, CDC13) &lt;5 177.5, 160.5, 157.7, 155.5, 152.7, 144.8, 144.3, 137.7, 130.1, 129.7, 121.7, 119.2, 114.6, 111.0, 110.2 , 109.0, 104.0, 103.9, 99.0, 77.7, 64.4, 63.8, 57.3, 55.2, 27.0; MS (ES+) m/z 432.0 (M + 1). Example 16.80 Γ-Methyl-4-phenoxy-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8,3'- Synthesis of 哚]-2'(1Ή)-ketone 143924-sp-20091127-6 -927- 201020257

According to the procedure as described in Example 16.79, and the insignificant change was made, the phenolic substitution of 3-methoxyphenol was used to obtain the fluorenyl _4-phenoxy 2,3-dihydrospiro [biting and argon [ 2,3-g][l,4]benzodioxanthene_8,3,_w哚]_2, (1 ketone (49%), colorless solid: 4 NMR (300 MHz, CDC13) δ 7.35-7.11 (m,3H), 6.93-7.04 (m, 1H), 6.76-6.63 (m, 3H), 6.54 (d, J = 8.4 Hz, 1H), 6.25 (s, 1H), 6.21 (s , 1H), 4.84 (ABq, 2H), 4.17-3.98 (m, 4H), 3.27 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 177.5, 156.4, 155.5, 153.0, 144.8, 144.3, 137.7 , 130.1, 129.3, 123.2, 121.4, 119.3, 118.2, 114.1, 111.0, 103.8, 99.0, 77.6, 64.4, 63.8, 57.4, 27.0; MS (ES+) m/z 402.0 (M + 1). Example 16.81 Γ-甲-4'-(3-morpholine-4-ylphenoxy)-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene Synthesis of -8,3'-吲哚]-2'(1Ή)-ketone

According to the procedure as described in Example W.79, and the insignificant change was made to replace 3-methoxyphenol with 3-morpholine, to obtain Γ-mercapto-4L (3-? 4-ylphenyloxy)_2,3_dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene 143924-sp.20091127^6 •928- 201020257 -8 , 3'-portion 哚]-2,(1Ή)-one (53%), as a colorless solid: 4 NMR (300 MHz, CDC13) (5 7.18-7.24 (m, 1H), 7.01-7.09 (m, 1H), 6.65 (d, J = 7.7 Hz, 1H), 6.55 (d, J = 8.5 Hz, 2H), 6.27 (s, 1H), 6.26-6.21 (m, 2H), 6.20 (s, 1H), 4.84 (ABq, 2H), 4.13-4.00 (m, 4H), 3.82-3.74 (m, 4H), 3.25 (s, 3H), 3.07-3.00 (m, 4H) ; 13C NMR (75 MHz, CDC13) &lt;;5 177.6, 157.5, 155.6, 153.3, 152.5, 144.8, 144.3, 137.6, 130.1, 129.7, 121.1, 119.4, 114.0, 111.0, 110.5, 109.7, 105.9, 103.6, 99.1, 77.6, 66.7, 64.4, 63.8, 57.3, 48.9, 27.0; MS (ES+) m/z 486.9 (M + 1). Example 16.82 4'-[(6-methoxypyridin-3-yl)oxy]-indole-methyl-2,3-di Synthesis of hydrogen snail [吱,[2,3-g][l,4] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one

Follow the procedure as described in Example 16.79 and perform irrelevant changes, φ replace 3-methoxyphenol with 6-methoxypyridine-3-yield, and replace 1-mercaptoimidazole with 1-butylimidazole , 4'-[(6-decyloxy-3-yl)oxy]-I1-indolyl-2,3-dihydrospiro[furo[2,3-g][l,4]benzene Dioxetemene -2]-2'(1Ή)-one (33%) ' is a colorless solid: iHNMR (300MHz, CDCl3) δ 7.64 (s, 1H), 7.27-7.18 (m, 1H), 6.91- 6.99 (m, 1H), 6.62-6.69 (m, 1H), 6.54-6.58 (m, 1H), 6.42-6.48 (m, 1H), 6.27-6.30 (m, 1H), 6.18-6.22 (m, 1H) ), 4.85 (ABq, 2H), 4.15-4.03 (m, 4H), 3.85 (s, 3H), 3.26 (s, 3H) ; 13C NMR (75 MHz, CDCI3) δ 177.4, 160.2, 155.5, 153.6, 147.5 , 144.9, 144.4, 137.8, 136.9, 143924-sp-20091127-6 • 929· 201020257 130.2, 130.1, 120.8, 119.2, 112.7, 111.0, 103.8, 99.1, 77.7, 64.4, 63.8, 57.3, 53.6, 27.0; MS ( ES+) m/z 432,9 (Μ + 1). Example 16.83 4'-(1,3-benzodioxanthene-5-yloxy)-indole-indenyl-2,3-dihydrospiro[吱,[2,3$][1, 4] Synthesis of benzodioxanthene-8,3'-吲哚]-2'(1'11)-one

Following the procedure as described in Example 16.79, and performing an insignificant change, the 3-methoxyphenol was replaced with benzo[d][l,3]dioxos--5-ol and 1-buten was used. Substituting 1-mercaptoimidazole for imidazole to obtain 4'-(1,3-benzodioxol-5-yloxy)-fluorenyl-indenyl-2,3-dihydrospiro 2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-indole (-)-one (8%) as colorless solid: 4 NMR (300 MHz, CDC13 δ 7.21 (s, 1H), 6.67-6.57 (m, 2H), 6.50 (d, J = 8.5 Hz, 1H), 6.32 (s, 1H), 6.25-6.15 (m, 3H), 5.89 (s, 2H), 4.84 (ABq, 2H), 4.18-4.04 (m, 4H), 3.26 (s, 3H); 13C NMR (75 MHz, CDC13) &lt;5 177.5, 155.6, 153.9, 150.9, 148.0, 144.8, 144.3 , 143.7, 137.7, 130.0, 120.6, 119.4, 113.1, 111.2, 111.0, 107.8, 103.4, 101.5, 101.4, 99.0, 77.5, 64.4, 63.9, 57.3, 27.0; MS (ES+) m/z 445.8 (M+l) . Example 16.84 4'-(4-Methoxyphenoxy)-indole-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene Synthesis of ene-8,3'-吲哚]-2\1Ή)-ketone 143924-SD-20091127-6 •930- 201020257

In a ι〇ml microwave reaction vessel, packed with 4, bromo-hydrazine, methyl-3,7-dihydro-2H-spiro[benzophenophene[5,6,4,2]dioxene terpene _8,3,_Dihydroindole-ketone (0.19 g, 0.5 mmol), 4-methoxyphenol (〇 12 g, i 〇 millimol), potassium butoxide (0.11 g, 1 〇 莫 )), copper bromide 1 (〇〇 12 g, 〇 (10) milli φ mol) and anhydrous 1-methyltetrahydropyrrol-2-one (2 ml). The reaction mixture was at 250 in a microwave reactor. (The next irradiation was carried out for 75 minutes and allowed to cool to ambient temperature. The reaction mixture was poured into water (15 ml) and extracted with ethyl acetate (5 mL). Washed with brine (5 ml), dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography eluting with 15% ethyl acetate in hexanes 50% gradient solution dissolved 'obtained 4'-(4-methoxyphenoxypurine, _mercapto-2,3-dihydrospiro[furo[2,3-g][l,4]benzoic Oxygen decene _8,3,-吲哚]-2,(1Ή)-one (0.084 succinyl, 39%) as an off-white solid: mp 55-58 ° C (ethyl acetate /hexane); NMR (300 MHz, CDC13) δ 7.27-7.14 (m, 1Η), 6.78-6.59 (m, 5H), 6.44 (d, J = 8.48 Hz, 1H), 6.31 (d, J = 1.08 Hz, 1H), 6.22 (d , J = 1.08 Hz, 1H), 4.86 (ABq, 2H), 4.16-4.03 (m, 4H), 3.74 (s, 3H), 3.26 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 177.6, 155.8, 155.6, 154.3, 149.6, 144.8, 144.3, 137.7, 130.0, 120.2, 120.1, 119.5, 114.5, 112.7, 111.0, 103.1, 99.1, 64.4, 63.9, 57.4, 55.6, 27.0 ; M S (ES+) m/z 432.0 (M + 1). Example 16.85 143924-sp-20091127-6 -931 - 201020257 Γ-Methyl-4-(p-pyridin-2-ylmethoxy)·2,3 Synthesis of dihydrospiro[p,pyrano[2,3 g][1,4]benzodioxanthracene -8,3'-吲嗓]-2,(1Ή)-one

In a 25 ml flask, packed with 4-hydroxy-indole-methyl-3,7-dihydro-2-indole-spiro[benzofuro[5,6-b][l,4]dioxanthene·8 , 3,_Dihydroindole]_2, ketone (33 g, 〇mole), 2-(bromohydrazinyl)pyridine hydrobromide (0.4 g, 1.6 mmol), carbonic acid (0.98 g, 3.0 mmol) and anhydrous n,N-dimethylformamide (6 mL) ❹. The reaction mixture was heated at 100 C for 1.5 hours and allowed to cool to ambient temperature & filtered. The filtrate was concentrated in vacuo and the residue was purified by column chromatography eluting with &lt;RTI ID=0.0&gt;&gt; -yloxy)-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxolene_8,3'_啕哚]-2' ( 1 Ή)-ketone (0.202 g, 49%) as an off-white solid: m.p. 181-183 ° C (decyl alcohol); WNMR (300 MHz, CDC13) δ 8.46 (d, J = 4.7 Hz, 1H), 7.56-7.60 ( m, 1H), 7.24-7.26 (m, 1H), 7.17-7.10 (m, 1H), 6.99 (d, J = 7.9 Hz, 1H), 6.66 (d, J = 8.5 Hz, 1H), 6.57 (d , ® J = 7.8 Hz, 1H), 6.44 (s, 1H), 6.25 (s, 1H), 5.14-5.01 (m, 2H), 4.86 (ABq, 2H), 5.18-4.99 (m, 1H), 4.17 -4.03 (m, 4H), 3.24 (s, 3H); 13 C NMR (75 MHz, CDCI3) δ ΠΊ.9, 156.7, 155.8, 154.3, 148.6, 144.5, 144.3, 137.8, 136.8, 130.3, 122.4, 120.7 , 119.8, 117.6, 111.4, 107.3, 102.0, 98.9, 77.5, 70.1, 64.5, 63.9, 57.4, 26.9; MS (ES+) m/z 417.0 (M + 1). Example 16.86 Methyl-bucket (4-fluorobenzyloxy)-2,3-dihydrospiro[N-[2,3-g][l,4]benzodiazepine 143924-sp-20091127-6 -932 · (S) 201020257 Synthesis of oxetene-8,3'-p?丨嗓]-2'(1Ή)-ketone

Obtaining 2-(bromomethyl)pyridinium hydrobromide using 1-(bromomethyl)-4-fluorobenzene according to the procedure described in Example 16.85 and performing an insignificant change Γ-Methyl-4-(4-fluorobenzyloxy)-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8, 3'-thirty 哚]-2'(lΉ)-one (62%) as a colorless solid: 1HNMR 10 (300 MHz, CDC13) δ 7.21-7.28 (m, 1H), 7.04-6.88 (m, 4H), 6.63 (d, J = 8.5

Hz, 1H), 6.56 (d, J = 7.8 Hz, 1H), 6.41 (s, 1H), 6.23 (s, 1H), 4.93 (ABq, 2H), 4.81 (ABq, 2H), 4.21-4.05 (m , 4H), 3.23 (s, 3H) ; 13C NMR (75 MHz, CDCI3) δ 177.9, 163.8, 160.6, 155.9, 154.5, 144.6, 144.3, 137.7, 132.1, 132.0, 130.1, 128.4, 128.3, 119.8, 117.9, 115.2, 115.0, 111.2, 107.5, 101.9, 99.0. 77.5, 68.9, 64.5, 63.9, 57.4, 26.9; MS (ES+) m/z 434.2 (M + 1). Example 16.87 4·-(4-Fluorophenoxy)-fluorene-methyl-2,3-dihydrospiro[1,3-g][l,4]benzodioxanthene -8,3'-Ling Duo]-2,(l,H)-ketone synthesis

F

(9) 哚]-ΑΓΗ)-ketone (41%), L-day mouth opening [2,3-g][l,4]benzodioxanthene-8,3,- is an off-white solid: melting point 15i-i53 °C (methanol); 143924-sp.20091127-6 -933- 201020257 1H NMR (300 MHz, CDC13) d 7.21-7.27 (m, 1H), 6.80-6.88 (m, 2H), 6.71-6.60 (m, 3H), 6.51 (d, J = 8.4 Hz, 1H), 6.25 (s, 1H), 6.17 (s, 1H), 4.83 (ABq, 2H), 4.14-4.01 (m, 4H), 3.26 (s, 3H 13C NMR (75 MHz, CDC13) 5 177.4, 160.2, 157.0, 155.5, 153.1, 152.4, 152.4, 144.9, 144.3, 137.7, 130.2, 121.5, 119.4, 119.3, 119.1, 115.9, 115.6, 113.9, 111.0, 104.0 , 99.0, 77.7, 64.4, 63.9, 57.3, 27.0; MS (ES+) m/z 420.0 (M + 1). Example 16.88 Γ-[(5-Gas-2-pyrimenyl)indolyl]-5-(6-methoxypyridin-3-yl)spiro[1-benzofuran-3,3'-oxime ]-2'(1Ή)-ketone synthesis

The 6-(dimethylamino)pyridin-3-yldihydroxy group was replaced with (6-methoxypyridin-3-yl)dihydroxyborane according to the procedure as described in Example 16.12, and the insignificant change was carried out. Borane and using 5-bromo-indenyl-[(5-carbyl-2-pyromenyl)methyl]spiro[1-benzofuran-3,3'-蚓哚]ΑΓΗ)-one to replace 4 '-Bromo-1,-[(5-carbyl-2-quinolyl)methyl]spiro[吱,[2,3-f][l,3]benzodioxolene-7 ,3,-蚓哚]-2'(1Ή)-嗣' obtained ι'_[(5_气基_2·pyromenyl)methyl]-5_(6-decyloxypyridyl) snail [ 1-benzofuran-3,3,-thracene]-2'(1Ή)-one (20%) as a colorless solid.··············· (d, J = 2.5 Ηζ, 1 Η), 7.54 (dd, J = 8.6, 2.2 Hz, 1H), 7.35 (dd, J = 8.4, 1.6 Hz, 1H), 7.27 (t, J = 7.7 Hz, 1H) , 7.17 (d, J = 7.3 Hz, 1H), 7.07-6.98 (m, 2H), 6.95 (d, J = 7.8 Hz, 1H), 6.88 (d, J = 2.2 Hz, 1H), 6.69 (d, J = 8.6 Hz, 1H), 5.12 (d, J = 15.8 Hz, 1H), 143924-sp-20091127-6 -934· 201020257 5.00 (d, J = 9.2 Hz, 1H), 4.91 (d, J = 15.8 Hz, 1H), 4.73 (d, J = 9.2 Hz, 1H), 3.8 9 (s, 3H) ; 13C NMR (75 MHz, CDC13) &lt;5 176.9, 163.2, 160.3, 144.5, 141.3, 137.2, 136.9, 132.2, 131.7, 130.1, 129.8, 129.6, 129.1, 128.5, 126.4, 126.0, 124.1, 123.9, 121.7, 110.9, 110.6, 109.0, 79.7, 60.4, 58.0, 53.5, 39.2; MS (ES+) 475.5 (M + 1), 477.5 (M + 1). Example 17 Γ-(4-Hydroxybenzyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3W| 哚]-2' (1Ή )-- Synthesis

Γ-[4-(yloxy)-yl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-啕哚] -2'(1Ή)-one (2.4 g '5.1 mmol) and a mixture of palladium/carbon (1% w/w, 0.49 g) in anhydrous methanol (10 ml) and ethyl acetate (50 ml) , hydrogenated at a cylinder temperature for 16 hours at ambient temperature. The mixture was filtered through a φ celite pad. The pad was washed with ethyl acetate (50 mL) and concentrated in vacuo. The residue was purified by column chromatography and eluted with ethyl acetate in a 25% to 50% gradient of hexane to give ι, _(4-benzyl)-5,6-dihydrospiro[benzene And [l,2-b: 5,4-b']difuran-3,3,-吲哚]-2,(1Ή)-one (1.86 g, 94%) ' is a colorless solid: melting point 226-227e ; iHNMRQOOMHz'CDCls) δ 7.25-7.13 (m, 4H), 7.06-6.99 (m, 1H), 6.87-6.82 (m, 1H), 6.78-6.72 (m,

2H), 6.44-6.41 (m, 2H), 5.27 (s, 1H), 4.88 (ABq, J = 69.0, 15.3 Hz, 2H), 4.84 (ABq, J = 82.9, 9.0 Hz, 2H), 4.55-4.46 (m, 2H), 2.96-2.86 (m, 2H) ; 13C 143924-sp-20091127-6 -935- 201020257 NMR (75 MHz, CDC13) 5 178.2, 161.8, 161.3, 155.5, 142.1, 132.8, 128.8, 128.7 , 127.5, 123.9, 123.5, 120.0, 119.9, 118.8, 115.8, 109.4, 93.3, 80.5, 72.4, 70.0, 57.8, 43.7, 28.9; MS (ES+) m/z 385.9 (M + 1). Example 17.1·(4-Hydroxyindenyl)-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene-83'-吲哚]-2 Synthesis of '(1'H)-ketone

According to the procedure as described in Example 17, and the inconsequential changes were made, 1'-[4-(yloxy)-yl-2,3-dihydrospiro[吱,[2,3-g] was used. ][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one substituted 1,-[4-(benzyloxy)hanyl]-5,6- Dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3·-吲哚]-2,(1Ή)-one, 1,-(4-hydroxybenzyl) -2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-啕哚]-2'(1Ή)-one ( 93%), as colorless solid: mp 243-244 ° C; WNMRGOO MHz, CDC 13) δ 9.42 (s, 1 Η), 7.30-7.22 (m, 1H), 7.20-7.13 (m, 3H), 7.05- 6.97 ( m, 2H), 6.76-6.68 (m, 2H), 6.52 (s, 1H), 6.04 (s, 1H), 4.89-4.63 (m, 4H), 4.21-4.07 (m, 4H) ; 13 C NMR ( 75 MHz, CDC13) 5 176.6, 156.7, 154.6, 144.1, 142.1, 137.7, 131.7, 128.6, 126.4, 123.5, 122.9, 121.2, 115.3, 110.8, 109.5, 98.8, 79.3, 64.1, 63.5, 57.1, 42.5; MS ( ES+) m/z 401.9 (M + 1). Example 17.2 Γ-(3-propyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3'-qiao嗓] Synthesis of ketone 143924-sp-20091127-6 -936- 201020257

According to the procedure as described in Example 17, and the insignificant change was made, Γ-[3-(yloxy)propyl]-2,3-dihydrospiro [bito-and-[2,3-g] was used. [l,4]benzodioxanthene-8,3'-indole]-2'(1Ή)-one substituted Γ-[4-(yloxy)indenyl]-5,6-dihydro Snail [benzo[1,2-b:5,4-b]difuran-3,3'-啕哚]-2'(1Ή)-one, Γ-(3-hydroxypropionyl)-2 ,3-diazaspiro[furo[2,3-g][l,4]benzodioxanthene-8,3'-蚓哚]-2'(1Ή)-one (83%): Melting point 157-158°C (ethyl acetate/hexane); 4 NMR (300 MHz, CDC13) δ Ί33-Ί.Π (m, 1H), 7.18-7.15 (m, 1H), 7.08-7.03 (m, 1H), 6.95-6.92 (m, 1H), 6.48 (s, 1H), 6.19 (s, 1H), 4.73 (ABq, 2H), 4.19-4.08 (m, 4H), 3.02-3.80 (m, 2H) , 3.61-3.55 (m, 2H), 2.98 (d, J = 6.0 Hz, 1H), 1.98-1.85 (m, 2H) ; 13C NMR (75 MHz, CDC13) ^ 178.8, 155.3, 144.6, 141.9, 138.3, 132.4, 128.9, 124.1, 123.6, 120.6, 111.4, 108.5, 99.4, 80.0, 64.5 63.9, 58.3, 58.1, 36.4, 29.8; MS (ES+) m/z 353.8 (M + 1). Example 18 2'-keto-2,3-dihydrospirofurfuro[2,3-g][l,4] benzodioxanthene _8,34 哚]-Γ(2Ή)- Synthesis of acid-lowering ethyl ester

In the water (Ν Ν-dimethyl decylamine (30 ml) in the cooled ((rc) suspension, add 143924-sp-20091127-6 -937- 201020257 plus 2,3- dihydro snail [吱And [2,3-g][l,4]benzodioxolene _83,_w 哚]-2(1 Η)-one (0.99 g, 3.39 mmol), followed by ethyl benzoate % ml, 3.7 millimoles). The reaction mixture was stirred at ambient temperature for 18 h and concentrated in vacuo. The residue was purified by column chromatography, and eluted with ethyl acetate in 5% to 66% gradient of hexane to give 2,- keto-2,3- snail [吱味[2 ,3-g][l,4]benzodioxanthene bado]_ι'(2,η)-rebel acid vinegar (0.68 g '55%) 'is a colorless solid: melting point ^200^ Alkane / ethyl acetate); NMR (300 MHz, CDC13) δ 7.96 (d, J = 7.7 ΗΖ, 1 Η), 7.39-7.34 (m, 1 Η), 7.19-7.18 (m, 2H), 6.50 (s, 1H ), 6.27 (s, 1H), 4.93 (d, J = ® 9.1 Hz, 1H), 4.63 (d, J = 9.1 Hz, 1H), 4.49 (q, J = 7.1 Hz, 2H), 4.21-4.18 ( m, 2H), 4.13-4.10 (m, 2H) 1.45 (t, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDC13) δ 175.7, 155.1, 150.8, 144.9, 138.7, 138.4, 130.7, 129.2, 125.5, 123.8, 121.0, 115.2, 111.7, 99.4, 80.8, 64.5, 63.9, 63.7, 58.6, 14.2; MS (ES+) m/z 367.7 (M + 1) 0 Example 18.1 4'-Momot-2'-Oxygen Synthesis of snail [吱,[2,3-f][l,3]benzodioxanthene-7,3'-嘀哚]-1'(2Ή&gt;carboxylic acid tert-butyl ester

❷

A 4'-Bromospiro[furo[2,3-f][l,3]benzodioxol-7,3'-峋哚]-2'(1Ή)-one (0.99 g) , 2.8 millimolar), di-tert-butyl dicarbonate (1.0 ml, 4.4 mmol) and sodium hydroxide (0.28 g, 6.9 mmol) and tetrahydrofuran/water 143924-sp-20091127-6 - 938-

(S201020257 (5/2, 46 ml) mixture was stirred at ambient temperature for 16 h. Part of tetrahydrofuran was removed in vacuo and mixture was extracted with ethyl acetate (4 X 50 mL). The combined organic extracts are dried over sodium sulfate, filtered, and concentrated in vacuo. The residue is purified by column chromatography and eluted with ethyl acetate ethyl acetate in 10% to 20% gradient of hexane. 4'-Bromo-2_-oxabuffo[2,3-f][l,3]benzodioxol-7,3M丨哚Η'(2Ή)-carboxylic acid third- Butyl ester (0.93 g '74%)' is a colorless solid: m.p., i.sup.54.sup.ssssssssssssssssssssssssssssssssssssssssssssssssssssssss J = 1.8

Hz, 1H), 7.32 (dd, J = 8.1, 8.1 Hz, 1H), 6.59 (s, 1H), 6.44 (s, 1H), 5.90 (d, J = 4.9 Hz, 2H), 4.79 (ABq, 2H ), 1.53 (s, 9H); 13 C NMR (75 MHz, DMSO-d6) δ 175.4, 157.1, 149.1, 148.8, 141.9, 141.8, 131.1, 129.1, 129.0, 119.0, 117.4, 114.5, 103.9, 101.9, 93.2 , 84.7, 78.7, 59.9, 28.1; MS (ES+) m/z 460.2 (M + 1), 462.2 (M + 1). Example 18.2 2·-keto-2,3-dihydrospiro[glamano[2,3_phantom [1,4]benzodioxanthene·8,34 哚]-1'(2Ή)- Synthesis of carboxylic acid tri-butyl ester

In 2'3-dihydrospiro[&gt;folmo[2 3_g][14]benzodioxolene-8,3,吲哚2 (1Ή)-one (2.00 g, 6 kn. ), triethylamine (1.6 ml, 11. mmol) and 4_(dimethylamino) pyridine (〇.〇2 g, 0.16 mmol) in hydrazine, Ν_dimethylformamide ( In a stirred solution of 30 ml), ditributyl dicarbonate 143924*sp-20091127-6 201020257 (2.50 g, 11.4 mmol) was added. The reaction mixture was stirred at ambient temperature for 5 hours. Diethyl acetate was diluted and washed with water and brine. The organic phase was dried over anhydrous sodium sulfate and filtered and evaporated. 1/3) dissolving to give 2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3,_p丨哚]]Γ(2Ή)-Resinic acid tert-butyl ester (2.12 g, 79%): melting point 171-172. (: (ethyl acetate / hexane); 4 NMR (300 MHz, CDC13) 5 7.91-7.88 (m,1Η), 7.36-7.29 (m,1H),7.16-7.14 (m,1H),6.47 (s,1H),6.39 (s,1H), 6.26 (s,1H), 4.75 ( ABq, 2 H), 4.19-4.08 (m, 4H), 1.62 (s, 9H); MS (ES+) m/z 417.9 (M + Ref 23). Example 19 1'-{[(3, 511, 5 &amp; 8 , 8 wang 8,8 匕)-2,2,7,7-tetramethyltetrahydro-3 £111-bis[1,3]dioxos(4,5-b:47-d []pyran-5-yl]methyl}-2,3-dihydrospirofurfuro[2,3-g][l,4] benzodioxanthene-8,3'-吲嗦]-2'(1Ή)-ketone synthesis

In 2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene-8,3,-啕哚]-2'(1Ή)-one (0.40克, 1.35 mmol; in a suspension of anhydrous N,N-dimethylformamide (30 ml), cesium carbonate (132 g, 4.06 mmol) was added and the reaction mixture was taken at ambient temperature and Stir under nitrogen for 1 hour. Then add a sputum clock (0.05 g '0.3 mmol) and 6-0-toluene 醯 _, 2,3,4-di-0-sub-940- 143924-sp-20091127-6 (8) 201020257 Propyl-α-D-semi-peripherylpyrazine (ο. % mL, 37 mmol), and the reaction mixture was stirred at 8 CTC for 72 h and concentrated in vacuo. The residue was triturated with ethyl acetate and filtered thru a pad. The filtrate was concentrated in vacuo, and the residue was purified by column chromatography eluting with 5% to 66% gradient of ethyl acetate in hexane to give Μ^^tetradecyltetrahydro-3aH - bis[1,3]dioxonate and [4,5_b: 4i,5,_d]pyranyl-5-yl]nonyl}-2,3-dihydrospiro[P-samarium [2, 3-g][l,4]benzodioxanthene _8,3'-吲哚]-2·(1Ή)-嗣(0.56 g, 77%), as colorless solid: melting point 112_118t: (B Sterols); 1H NMR (300 MHz, CDC13) (5 7.29-7.21 (m, 1 Η), 7.12-7.08 (m, 1 Η), 7.02-6.95 (m, 2H), 6.55-6.31 (m, 2H), 5.48-5.42 (m, 1H), 4.91-4.82 (m, 1H), 4.68-4.59 (m, 2H), 4.33-4.22 (m, 3H), 4.18-4.10 (m, 4H), 4.07-3.98 (m , 1H), 3.88-3.80 (m, 1H), 1.38-1.26 (m, 12H) ; 13C NMR (75 MHz, CDC13) δ 177.7, 177.6, 155.3, 154.9, 144.4, 144.3, 143.0, 142.9, 138.3, 138.0 , 132.6, 132.1, 128.5, 128.4, 123.6, 123.2, 122.9, 122.8, 121.7, 121.0, 112.4, 111.9, 109.7, 109.6, 109.5, 109.2, 109.0, 108.8, 99.1, 99.0, 96.4, 96.2, 80.3, 79.6, 71.6 , 71.5, 71.0, 70.9, 70.5, 70.2, 65.9, 65.2, 64.5, 63.8, 57.9, 57.8, 41.0, 40.8, 26.1 , 26.0, 25.8, 25.5, 25.0, 24.5, 24.5; MS (ES+) m/z 538.0 (M + 1) ° Example 20 6-Deoxy-6-(2'-keto-2,3-dihydrospiro [Combustion of benzo[2,3$][1,4]benzodioxanthene -8,3'-p5j111]-1'(2Ή)-yl)-D-galacto-halose

-941- 143924-sp-20091127-6 201020257 Let l'-{[(3aR,5R,5aS,8aS,8bR)-2,2,7,7-ra methyltetrahydro-3aH_bis[(3) oxygen Oxene [4,5-b : 4,,5,-d]pyran-5-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][1 , 4] stupid and dioxin terpenes]-2,(1Ή)-one (0.45 g, 0.83 mmol) suspended in 80% ν/ν aqueous trifluoroacetic acid solution (4 mL), and The reaction mixture was stirred at ambient temperature for 3 hours. The reaction mixture is concentrated in vacuo, and the residue is recrystallized from ethanol to give 6-deoxy-(2, keto-2,3-dihydrospiro [taste &quot; Nanhe [2, 3-g] [l,4]benzodioxanthene oxime]-1,(2Ή)-yl)-D-semi-milk sucrose (0.025 g '7%), as an off-white solid: melting point (ethanol), 3C NMR (75 MHz, CDC13) &lt;5 178.5, 155.2, 155.2, 155·1, 155.0, © 144.5, 142.6, 142.2, 142.1, 138.0, 138.0, 132.3, 132.0, 129.0, 123.5, 123.4, 121.0, 120.9, 111 · 6, 111.4, 109.9, 109.7, 99.2, 92.7, 79.9, 64.4, 63.8, 60.4, 58.0, 21.0, 14.2; MS (ES+) m/z 480.0 (Μ + 23). Example 21 Synthesis of 1·-cyclopropyl-2,3-dihydrospiro[,4,3-g][l,4]benzodioxolene-8,3ι_,5|

In 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3,-啕哚]-2'(1Ή)-one (0.59 g, 2.0 mmol, cyclopropyldihydroxyborane (0.34 g, 4.0 mmol), copper acetate (0.36 g, 2.0 mmol) and 4-(Ν,Ν-dimethylamino) Adding hexamethyldisulfonium nitride (1 Μ in tetrahydrofuran 143924-sp-20091127) in a suspension of pyridine (0.73 g '6.0 mmol) in anhydrous benzene (1 mM) -6 -942- 201020257 liquid, 2.0 liters, 2.00 m.) The reaction vessel was fitted with a condenser with a calcium chloride drying tube at the top, and the mixture was heated at 95 t for 16 hours to cool the reaction mixture. The mixture was diluted with EtOAc (2 mL EtOAc) (EtOAc)EtOAc. Concentrate in vacuo. The residue was crystalljjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjjj Luyuan _8,3,_啕嗓]_2'(1Ή)-ketone (0.48g , 72%) 'is an off-white solid: melting point 227_228. (acetic acid ethyl acetate / diethyl ether); A NMR (300 MHz, CDC13) 5 7.36-7.28 (m, 1 Η), 7.18-7.11 (m, 2H) , 7.08-7.02 (m, 1H), 6.48 (s, 1H), 6.14 (s, 1H), 4.88 (d, J = 8.9 Hz, 1H), 4.62 (d, J = 8.9 Hz, 1H), 4.20- </ RTI> <RTIgt; 123.3, 121.3, 111.4, 109.7, 99.4, 80.1, 64.6, 64.0, 58.1, 22.5, 6.4; MS (ES+) m/z 336.0 (M + 1). Example 22 ®Γ-Ethyl-2,3- Synthesis of Hydronose [furo[2,3-g][l,4]benzodioxanthene-8,3,-吲哚]-2'(1Ή)-one

2,3-Dihydrospiro[1,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one (1.00 A mixture of gram, 3.39 mmol, sodium acetate (0.556 g, 6.78 mmol) and acetic anhydride (20 mL) was heated under reflux for 0.5 h. The reaction 143924-SP-20091127-6 -943- 201020257 was cooled to ambient temperature and concentrated in vacuo. The residue was triturated in water (2 mL) and then recrystallized from solid solid /hexanes to afford s. 1,4]benzodioxanthene-8,3'-key oxime]-2'(oxime)-one (0.802 g, 70%) as a colorless solid: mp 236-238. (: (hexane/diethyl ether); 4 NMR (300 MHz, CDC13) δ 8.32-8.25 (m, 1 Η), 7.42-7.33 (m, 1H), 7.25-7.15 (m, 2H), 6.52 (s, 1H ), 6.25 (s, 1H), 4.97-4.90 (m, 1H), 4.68-4.60 (m, 1H), 4.25-4.04 (m, 4H), 2.68 (s, 3H) ; 13 C NMR (75 MHz, CDC13) δ 178.5, 171.0, 155.2, 145.1, 139.6, 138.6, 130.8, 129.4, 126.2, 123.7, 121.0, 116.8, 111.7, 99.6, 80.9, 64.6, 64.0, 58.8, 26.7; MS (ES+) Φ m/z 360.1 (M + 23). Example 23 1'-{[4-(Trifluoromethyl)pyridin-2-yl]indolyl}-2,3-dihydrospiro[吱,[2,3-g ][l,4] Synthesis of benzodioxanthene-8,3'-啕哚]-2'(1Ή)-_

22,3-二虱螺[吱咕,[2,3-g][l,4]benzodioxene _8,3,_μ丨嗓]_ 2 (1 Η)-ketone (0.753克 '2.55 house Moer), [4-(trioxymethyl) 唆 __2_ yl] sterol (Ashimori et al, C / iem. corpse Aflrm. (1990) 38 : 2446-2458) (0.655克, 3.70 mmol, and tri-n-butylphosphine (0.93 ml, 37 mmol) in anhydrous tetrahydrofuran (20 mL) and anhydrous hydrazine (0.2 mL) at ambient temperature Add a solution of azobis- trespodic acid (〇·64 ml, 4.1 mmol) in anhydrous tetrahydrofuran (10 ml) over a period of 1 min. • 944- 143924-sp-20091127-6

(S 201020257 The reaction mixture was stirred at rt EtOAc (3 mL). Dehydrated with anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography eluting with EtOAc EtOAc Dissolve in a gradient of 0% to 20% in methylene chloride and recrystallize from methanol to obtain 1-{[4-(difluoromethyl)-bito-2-yl]methyl}-2,3- Dihydrospiro[吱,[2,3-g][i,4] benzodioxanthene-8,3'-thirsty]-2,(1Ή)-one (0.164 g, 10%) , colorless® solid: melting point ^4-155^ (methanol); 1H NMR (300 MHz, CDC13) &lt;5 8.76 (d, J = 5.1 Hz, 1H), 7.51 (s, 1H), 7.44 (d, J = 5.1 Hz, 1H), 7.24-7.16 (m, 2H), 7.08-7.01 (m, 1H), 6.86 (d, J = 7.7 Hz, 1H), 6.52 (s, 1H), 6.31 (s, 1H ), 5.27 (d, J = 16.1 Hz, 1H), 5.04 (d, J = 16.1 Hz, 1H), 4.95 (d, J = 9.0 Hz, 1H), 4.69 (d, J = 9.0 Hz, 1H), 4.23-4.11 (m, 4H) ; 13C NMR (75 MHz , CDC13) δ 177.8, 157.3, 155.3, 150.8, 144.8, 141.9, 139.8, 138.5, 132.3, 129.0, 124.1, 123.9, 121.1, 118.7, 117.6, 111.8, 109.3, 99.5, 80.1, 64.7, 64.0, 58.2, 45.8; MS (ES+) m/z 455.0 (M + 1). Example 24 4·-Ethyl-1·-methyl-2,3-dihydrospiro[sn-[2,3-g][l, 4] Synthesis of benzodioxanthene-8,3'-(tetra)indole-2'(1Ή)-one

4'-bromo-indenyl-indenyl-2,3-dihydrospiro[furo[2,3$][1,4]benzophenone was packed in a 10 ml vial-terminated microwave pressure-resistant tube. Dioxetene-8,3'-吲143924-sp-20091127-6 -945- 201020257 哚]-2'(1Ή)-ketone (0.39 g, 1.0 mmol), palladium acetate (Π) (0.022克, (^ mmol), 1,3-bis(diphenylphosphino)propene (0.10 g, 0.25 mmol) and potassium carbonate (0.17 g, 1.2 mmol). Cap the tube, The mixture was dried with nitrogen for 5 minutes, and butyl vinyl ether (0.52 ml, 4.0 mmol), hydrazine, hydrazine-dimethylformamide (2.0 ml) and water (0.2 ml) were added. Heated under microwave irradiation (100 W, 120 ° C) for 1 hour, and allowed to cool to ambient temperature, poured into 10% v / v aqueous hydrochloric acid (5 ml), and mixed at ambient temperature for 1 hour. It was diluted with water (20 ml) and neutralized with a 2M aqueous sodium carbonate solution. ethyl acetate (20 ml) was added, and the mixture of the two phases was passed through 石 藻 φ φ 。 。. Wash the tablets and transfer the mash to the separatory funnel. Acetic acid The combined organic extracts were washed with water (3×20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by column chromatography eluting with a gradient of 0% to 100% of ethyl acetate in hexanes, then recrystallised from dichloromethane to diethyl ether Base 2,3_ dihydrospiro[吱°南和[2,3-g][l,4]benzodioxanthene]2'(ΓΗ)-ketone (0.264 g, 75%) , as an off-white solid: mp 234-235 ° C (di-methane / ethyl ether); 1H NMR (300 MHz, CDC13) ά 7.55-7.44 (m, 2H), 7.14-7.08 (m, 1H), 6.50 (s , 1H), 5.99 (s, 1H), 4.95-4.77 (m, 2H), 4.19-4.04 (m, 4H), 3.28 (m, 3H), 2.43 (m, 3H) ; 13 C NMR (75 MHz, CDC13) 6 198.3, 178.6, 157.2, 145.4, 144.3, 137.4, 134.5, 130.6, 129.5, 124.4, 119.9, 112.1, 110.2, 98.9, 78.9, 64.5, 64.0, 59.4, 28.5, 27·0; MS (ES+) m /z 351.8 (M + 1). Example 25 1 -Methyl-4'-(2-methyl-1,3-indolyl)-sialt-4-yl)-2,3-dihydrospiro[Nit-[2,3-g][l , 4] benzene 143924-sp-20091127-6 -946- 201020257

4'-(Bromoethenyl)-1,-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8 ,3,-吲哚]-2,(1Ή)-one (0.25 g, 0.57 mmol) in a suspension in p-dioxane (15 ml), thioacetamide (0. Q47 g, ® 0.63 mmol, and the reaction mixture which became homogeneous upon heating was heated at 80 ° C for 1 hour. The reaction mixture was allowed to cool to ambient temperature and concentrated to dryness in vacuo. &lt;RTI ID=0.0&gt;&gt; Methyl-4,-(2-mercapto-1,3-pyrazol-4-yl)-2,3-dihydrospiro[Ethylene[2,3-g][l,4]benzoic Oxygen decene-8,3·-吲哚]-2'(1Ή)-one (0.076 g, 33%) as an off-white solid: mp 219-220 ° C (hexane / ethyl acetate); 1H NMR (300 MHz, CDC13) 5 7.42-7.36 (m, 1Η), 7.32-7.27 (m, 1H), 6.91 (d, J = 7.7 Hz, 1H), 6.54 (s, 1H), 6.36 (s, 1H) , 6.22 (s, 1H), 4.81-4.71 (m, 2H), 4.21-4.07 (m, 4H), 3.29 (s, 3H), 2.64 (s, 3H) ; 13C NMR (75 MHz, CDC13) δ 178.4 , 165.2, 156.1, 151.8, 144.4, 137.7, 133.2, 129.2, 128.6, 124.7, 122.2, 116.6, 111.2, 108.2, 99.1, 78.3, 77.4, 64.7, 64.0, 58.8, 27.0, 19.1; MS (ES+) m/z 406.9 (M + 1). Example 26 4'-(2-Amino-1,3-oxazol-4-yl)-indole-indenyl-2,3-dihydrospiro[唉,[2,3-g][l,4 Synthesis of benzodioxanthene-8,3W丨哚]-2'(1Ή)-one 143924-sp-20091127-6 • 947- 201020257

4, 曱 · 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 Ή)-ketone (0.20 g, 0.47 mmol) in a solution of anhydrous ethyl acetate (ίο ml), thiourea (〇〇 39 g, 〇 51 mmol), and the reaction mixture was heated under reflux Hour. The reaction mixture was allowed to cool to ambient and concentrated in vacuo to dryness. The crude product was purified by column chromatography and eluted with 〇% to 1% by weight of methanol in dioxane, and 4-(2-amino-1,3-; -yl)-1'-mercapto-2,3-dihydrospiro[&gt;follow[2,3-§][1,4] Ben-Oxygen Park Rare-8,3^5丨嗓-2'(1Ή)-ketone (0.159 g, 84%) as a pale yellow solid: mp 233-234 ° C (decomposition) (dioxane / decyl alcohol); iHNMR (3 〇〇 MHz, CDC13) (5 7.44-7.37 (m, 1H), 7.23 (d, J = 7.9 Hz, 1H), 6.95 (d, J = 7.9

Hz, 1H), 6.57-6.42 (br m, 2H), 6.37 (s, 1H), 6.22 (s, 1H), 5.80 (s, 1H), 4.80-4.73 (m, 2H), 4.22-4.07 (m , 4H), 3.28 (s, 3H) ; 13C NMR (75 MHz, CDCI3) δ 178.0, 168.2, 155.7, 144.8, 144.4, 138.1, 129.7, 129.4, 124.3, 121.9, 111.4, 109.4, 105.9, 99.2, 78.4, 77.4, 64.7, 64.0, 58.6, 27.1; MS (ES+) m/z 408.3 (M + 1) 0 Example 27 4·-(5-Hydroxy-1H-pyrazol-3-yl)-1·-methyl- Synthesis of 2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3%5 卜多]-2·(1Ή)-ketone synthesis 143924 -sp-20091127-6 -948 - 201020257

4'-(Mosyl acetyl)-1,-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8 , 3·- 哚 哚]-2'(1Ή)-one (0.23 g, 0.53 mmol) in a suspension in glacial acetic acid (5 ml), dropwise addition of hydrazine hydrate (〇.〇 3 ml, 59.59 mmol) and the reaction mixture was heated under reflux for 16 hours, allowed to cool to ambient temperature and concentrated in vacuo. The crude product was triturated in di-methane (1 mL) and the solid formed was recrystallised from di-methane/diethyl ether. After the second recrystallization from methanol, 4,-(5-hydroxy-1Η-pyrazol-3-yl)-indole-methyl-2,3-dihydrospiro[吱,[2,3- g][l,4]benzodioxanthene-8,3·-呻哚]-2'(1Ή)-brewed] (0.029 g, 14%), colorless solid: melting point &gt;250 ° C (methanol); ^ NMR (300 MHz, DMSO-d6) 5 11.77 (br s, 1H), 9.51 (br s, 1H), 7.49- 7.39 (m, 1H), 7.22-7.09 (m, 2H), 6.41 (s, 1H), 6.15 (s, 1H), 4.76-4.42 (m, #3H), 4.25-4.02 (m, 4H), 3.19 (s, 3H) ; 13C NMR (75 MHz, DMSO-de) δ 177.1, 155.0, 144.7, 144.0, 137.2, 129.1, 126.5, 123.1, 121.8, 110.6, 108.8, 98.7, 90.6, 76.2, 64.2, 63.6, 57.7, 26.5; MS (ES+) m/z 391.8 (M + 1). Example 28 143-(3-Methyl-1,2,4-oxadiazol-5-yl)benzyl]-2,3-dihydrospiro[吱,[2,3-g][l,4 Benzodioxanthene _8,3·_吲哚; μ2'(1Ή), synthesis 143924-sp-20091127-6 -949· 201020257

_8,3·'嗓]4,(2Ή)·yl)methyl]benzamide (0.50 g, U7 mmol) and N,N-monomethylacetamide dimethyl acetal (〇. A solution of 6 mL (41 mL) in EtOAc, EtOAc (EtOAc)EtOAc. Then add hydroxylamine hydrochloride 1 u❹g, L6 mmol, 丄, 4·dioxane (1 mL), glacial acetic acid (10 mL) and 2M aqueous sodium hydroxide (〇.85 mL, 17 〇 Mohr) and the mixture was heated at 90 C for 2 hours. The mixture was allowed to cool to ambient temperature&apos; and water was added, causing deposits to deposit. The solid was collected by filtration, washed with water and hexane, and recrystallized from dioxane/hexane to give rP-G-methyl 4,2,4-oxadiazol-5-yl) 2,3-di-spiro[吱,[2,3-g][i,4]benzodioxolene-8,3,_吲嗓]-2'(1Ή)-one (0.038 g) , 6%), as colorless solid: melting point 8〇-89°C (di-methane/hexane); 4 NMR (300 MHz, CDC13) 5 8.09-8.12 (m, 2H), 7.54-7.57 (m, 2H), 7.15-7.18 (m, 2H), 7.00-7.03 (m, 1H), 6.74-6.77 (m, 1H), 6.50 (s, 1H), 6.29 (s, 1H), 5.14-5.17 (m, (H), 4. , 167.9, 155.3, 144.7, 141.7, 138.4, 137.0, 132.3, 131.4, 129.9, 128.9, 127.4, 126.8, 124.8, 124.1, 123.7, 120.8, 111.6, 109.1, 99.5, 80.2, 64.5, 63.9, 58.1, 43.7, 11.7 MS (ES+) m/z 467.8 (M + 1). Example 29 143924-sp-20091127-6 -950- 201020257 3-{4-[(3-Methyl-2'-oxaspiro[吱-[and 如 benzoisoxazole_5,3,_p? Synthesis of hydrazine, (2Ή)-yl)methylphenylpyridinium-3-mercaptopropanonitrile

3-methylspiro[ρ矢降和[3,2-f][l,2]苯苯异ρ号β坐_5,3Ί ρ来]_2,(ιή)-ketone (0.35g' 1.20m In a solution of anhydrous ν, Ν-dimethyl decylamine (20 ml), sodium hydride (60% w/w dispersion in mineral oil) was slowly added at 〇 ° C. 0.072 grams, 1.50 millimoles). The solution was stirred at ambient temperature for 30 minutes to add 5-(4-(bromomethyl)phenyl)iso-π-salt (as also known as Md. C/zem. [Hungry (1998) 8: 2241-2246) (0.24 g, 1.00 mmol) and the mixture was stirred at ambient temperature for 16 hours. The reaction mixture was poured into water (200 mL) The combined organic extracts were washed with brine (3×100 mL), dried over magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography and eluted with a 15% to 50% gradient of ethyl acetate in hexane to give 3-{4-[(3-methyl-2,-oxo[ Oligo[3,2-f][l,2]benzisoxazole-5,3,-吲哚]-Γ(2Ή)-yl)indolyl]phenyl}-3-ketopropanonitrile (0.33 g, 61%) as colorless solid: 4 NMR (300 MHz, CDC13) δ 7.96-7.92 (m, 2H), 7.63-7.60 (m, 2H), 7.50-7.46 (m, 1H), 7.23- 7.13 (m, 2H), 7.046.97 (m, 2H), 6.71-6.67 (m, 1H), 5.43-4.76 (m, 4H), 4,06 (s, 2H), 2.46 (s, 3H). Example 29.1 144-(3-Amino-1H-pyrazol-5-yl)-yl]-3-methylspiro[吱,[3,2-f][l,2]benzene 143924-sp.20091127 -6 -951- 201020257 and isoxazole-5,3,2 5丨哚]-2' (1' ketone hydrochloride synthesis

1.6 HCI NH2 in 3-(4-((3-mercapto-2l keto-6H-spiro[benzofuro[5,6_d]isoxazole_5,3,_dihydroindole]-Γ- a solution of hydrazino)phenyl)-3-ketopropanonitrile in ethanol (20 ml) 'add hydrazine hydrate (〇·4 〇ml, 15 mmol) ^heat the solution under reflux 4 Hour 'cool it to ambient temperature and concentrate in vacuum. The solid formed was dissolved in anhydrous decyl alcohol (10 ml), and a saturated solution (1.5 ml) of hydrogen chloride in anhydrous methanol was added to cause deposits. The solid was collected by filtration to obtain 1·-[4-(3-amino-1H-pyrazol-5-yl)octyl]-3-methylspiro[吱,[3,2-f][l , 2] benzoisoxazole-5,3'-啕哚]-2'(1Ή)-one (0.14 g '43%), as pale yellow solid: mp 191-195 ° C (methanol); 1 H NMR (300 MHz, DMSO-d6) δ 7.82-7.71 (m, 3 Η), 7.52 (d, J = 8.3 Hz, 2H), 7.31-7.18 (m, 2H), 7.10 (d, J = 8.6 Hz, 1H ), 7.04-6.97 (m, 2H), 6.40 (s, 1H), 5.16 (d, J = 16.3 Hz, 1H), 5.05 (d, J = 9.7 Hz, 1H), 4.98-4.89 (m, 2H) , 2.42 (s, 3H) ; 13 C NMR (75 MHz, DMSO-de) δ 176.3, 164.3, 157.8, 155.9, 145.7, 142.7, 138.0, 130.5, 129.7, 128.3, 127.5, 126.6, 124.7, 124.4, 123.8, 117.8, 109.2, 108.5, 108.4, 81.5, 56.1, 43.5, 9.8; MS (ES+) m/z 463.9 (M + 1). For C27H21N503 · 1.6 HCI: C, 62.15; H, 4.37; N, 13.42. Found: C, 61.97; H, 4.52; N, 13.15. Example 29.2 143924-sp-20091127-6 -952- 201020257 l'-[4-(3-Amine_1H_,Bizozole-5-yl)hanyl]_2,3_Dihydrospib-indol [wg Synthesis of Guanqi and Dioxodecene-8,3'-啕哚]-2'(1Ή)-ketohydrochloride

Follow the procedure as described in Example 29 and Example 29, 1 and perform irrelevant changes 'using 2,3-dihydrospiro[,,[2,3-g][l,4]benzo Dioxetemene-8,3'-吲哚]-2'(ΓΗ)-one replaces 3-methylspiro[吱,[3,2-f][l,2] benzisoindole- 5,3'-吲哚]-2'(ΓΗ)-ketone, which gives 1,-[4-(3-amino-1H-pyrazol-5-yl)benzyl]-2,3-dihydrospiro [furo[2,3-g][l,4]benzodioxanthene·8,3,_啕哚]-2'(1Ή)-one hydrochloride (25%), light yellow Solid: melting point 198-2 〇 rc (sterol); 1H NMR (300 MHz, DMSO-d6) 5 7.79 (d, J = 8.3 Hz, 2H), 7.43 (d, J = 8.3 Hz, 2H), 7.21- 7.25 (m, 1H), 7.15 (d, J = 7.1 Hz, 1H), 7.00 (t, J = 7.8 Hz, 2H), 6.50 (s, 1H), 6.38 (s, 1H), 6.08 (s, 1H) ), 5.06-4.86 (m, 2H), 4.80 (d, J = Q 9.3 Hz, 1H), 4.66 (d, J = 9.3 Hz, 1H), 4.21-4.01 (m, 4H) ; 13C NMR (75 MHz , DMSO-d6) δ 177.3, 155.2, 145.6, 144.7, 142.6, 138.3, 138.3, 132.2, 129.3, 128.4, 127.6, 126.7, 124.2, 123.7, 121.6, 111.4, 109.9, 99.3, 80.0, 64.7, 64.1, 57.7, MS (ES+) m/z 467.0 (M+l). For C27H22N404 ·1.5Ηα: C, 62.22; H, 4.54; N, 10.75. Found: C, 62.19; H, 4.59; N, 10.55. Example 30 l'_[4_(3_Indolyl-1,2,4-oxadiazol-5-yl)-yl]-2,3-dihydrospiro [biting and 143924-sp-20091127-6 • 953· 201020257 [2,3-g][l,4]benzodioxanthene _8,3L♦multiple]·2,(1Ή)__

4-[(2'-keto-2,3-dihydrospiro[2,3_g][14]benzodioxanthene-8,3'-ten]-1' ( 2Ή)-yl)mercapto]benzoic acid (〇75g, 丄7mmol) in a solution of di-methane (ίο ml), added gasified grasshopper (0 50 ml, 5 77 mmol) ) with N,N-dimethylformamide (2 drops, catalytic amount). The mixture was stirred at ambient temperature for 16 hours and concentrated in vacuo. The residue was dissolved in pyridine (1 mL) and transferred to a &lt;RTI ID=0.0&gt;&gt; To this solution, hydroxyacetamidine (25 g, 3.4 mmol) was added and the reaction mixture was placed in a microwave reactor at 17 Torr. Take a squat for 30 minutes. The reaction mixture was cooled to ambient temperature, concentrated in vacuo and purified eluting elut elut elut elut eluting elut Recrystallization, giving 144-(3-mercapto-1,2,4-oxadiazol-5-yl)indolyl]-2,3-dihydrospiro[吱味和参[2,3-g] [l,4]benzodioxanthene _8,3,_吲哚]_2, (1, 嗣_嗣(〇5〇g, 63%), colorless solid: melting point 177-178°C ( Dioxethane); 1H NMR (300 MHz, CDC13) δ 8.08 (d, J = 8.1 Hz, 2H), 7.46 (d, J = 8.1 Hz, 2H), 7.26-7.13 (m, 2H), 7.06-6.98 (m, 1H), 6.74 (d, J = 7.6 Hz, 1H)S 6.49 (s, 1H), 6.21 (s, 1H), 5.14 (d, J = 16.0 Hz, 1H), 4.94 (d, J = 9.0 Hz, 1H), 4.87 (d, J = 16.0 Hz, 1H), 4.66 (d, J = 8.9 Hz, 1H), 4.21-4.07 (m, 4H), 2.44 (s, 3H) ; 13C NMR (75 MHz, CDCI3) 5 177.6, 174.9, 167.8, 155.3, 144.7, 141.7, 138.4, 132.2, 143924-sp-20091127-6 954 (S) 201020257 128.9, 128.6, 128.0, 124'1, 123.8, 123.8, 120.8, 111.5 , 109.1, 99.5, 80.1, 64.5, 63.9, 58.1, 43.9, 11.7 ; MS (ES+) m/z 467.9 (Μ + 1) Example 31 2'-Mercapto-1·-(10)decylmethyl)-indole, 2,2,,3_tetrahydrospiro[cough and cation] benzodioxanene-8,3,- Qiao哚]-5'-carboxyguanamine synthesis

In the 2'-keto group (pyridine-2-ylmethyl itetrahydrospiro[furo[2,3 g] [1,4] benzodioxanthene _8,3'_呻哚]_5, - hydrazine (24 g, 〇 57 mmol) In a suspension of ethanol (20 ml), add 3 Μ aqueous sodium carbonate (2 ml) and 30% w/w aqueous hydrogen peroxide (2 ml) The reaction mixture was stirred at ambient temperature for 16 hours and concentrated in vacuo. The residue was purified in water to give 2'-keto-indole-(pyridin-2-ylmethyl)-1,2 ,2,,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3,_吲哚]_5, carboxycarboxamide (〇23克, 93%), as a colorless solid: m.p. 220-222°C (water); iHNMRQOOMI^CDClO (5 8.46-8.42 (m, 1H), 7.82 (s, 1H), 7.81-7.74 (m, 2H), 7.65 (d, J = 1.5 Hz, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.28 (dd, J = 7.0, 5.0 Hz, 1H), 7.19 (s, 1H), 6.98 (d, J =8.3 Hz, 1H), 6.50 (s, 1H), 6.33 (s, 1H), 5.14-4.97 (ABq, 2H), 4.81-4.68 (ABq, 2H), 4.19-4.06 (m, 4H) ; 13 C NMR (75 MHz, CDC13) δ 177.6, 167.6, 155.4, 155.1, 149.7, 145.7, 144.7, 138.3, 137.6, 132.4, 129.4, 129 .2, 123.3, 123.3, 122.3, 121.6, 112.1, 109.3, 99.2, 79.8, 64.7, 64.1, 57.7, 45.3; MS (ES+) m/z 429.9 (M + 1) 〇143924-sp-20091127-6 -955 · 201020257 Example 32 14(6-4 ^ .3-^ )f ^ ^ ^ ^ ^ ^ TT- A preparation of Tt ^ straight) Shang Yan Λ α.

In a 10 ml microwave reaction vessel, packed with Γ[[6-carbopyridine-3-yl)methyl]-2,3-dihydrospiro[吱喃和阳观...benzodioxanene-8,3 ,... 哚]-2, (1Ή)-ketone (0.13 g, 0.31 mmol) with morphine (〇 5 ml, 6 丨 millimolar). The reaction mixture was placed in a microwave reactor at 18 Torr. Irradiate for 2 minutes. The reaction mixture was poured into a mixture of water (15 ml) and ethyl acetate (3 ml). The layers were separated and the aqueous extracted with ethyl acetate (2 EtOAc). The combined organic layers were washed with EtOAc EtOAc m. The residue was purified by column chromatography and eluted with 50% ethyl acetate in hexane to give i, hepta-6- phenanthroline.

咬-3-yl) fluorenyl]-2,3-dihydrospiro|&gt; mercapto[2,3-g][l,4]benzodioxanthene -8,3. -2'(1Ή)-one (0.13 g, 92%) as colorless solid: m.p. 117. 119. NMR; NMR (300 MHz, DMSO-d6) δ 8.22-8.19 (m, 1H), 7.56-7.49 (m , 1H), 7.32-7.24 (m, 1H), 7.18-7.08 (m, 2H), 7.06-6.99 (m, 1H), 6.87-6.80 (m, 1H), 6.52 (s, 1H), 6.02 (s , 1H), 4.81 (q, J = 15.5 Hz, 2H), 4.72 (ABq, J = 40.6, 9.3 Hz, 2H), 4.22-4.06 (m, 4H), 3.70-3.63 (m, 4H), 3.44- 3.38 (m, 4H); 13 C NMR (75 MHz, DMSO-d6) (5 176.6, 158.5, 154.6, 146.7, 144.1, 141.9, 137.7, 137.1, 131.7, 128.7, 123.6, 123.0, 121.1, 121.0, 110.8, 109.4, 107.1, 143924-sp-20091127-6 - 956 - 201020257 98.8, 79.3, 65.8, 64.1, 63.5, 57.1, 45.0 ; MS (ES+) m/z 471.9 (Μ + 1). Example 32.1 1 -{[6 -(dimethylamino)p-pyridin-3-yl]methyl b 2,3·dihydrospiro[吱,[2,3_g][i,4] 本弁'一氧陆园稀嗓]- 2'(1Ή)-嗣 synthesis

® Following the procedure as described in Example 32, and performing irrelevant changes, replacing the ruthenium with diammonium (40% w/w 'in water) to obtain 1, 丨 [6_(diguanamine hydrazine) Pyridin-3-yl]methyl}-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene-8,3 ·-啕哚]- 2·(1Ή)-ketone (82%) ' is a colorless solid: melting point 93-95. (:; !H NMR (300 MHz, DMSO-d6) δ 8.18-8.14 (m, 1 Η), 7.49-7.43 (m , 1H), 7.31-7.24 (m, 1H), 7.18-7.07 (m, 2H), 7.05-6.98 (m, 1H), 6.65-6.59 (m, 1H), 6.52 (s, 1H), 6.02 (s , 1H), 4.87-4.62 (m, 4H), 4.21-4.07 (m, 4H), 2.98 (s, 6H); 13C NMR (75 MHz, DMSO-d6) d 176.6, 158.4, 154.6, 146.9, 144.1, 141.9, 137.7, 136.7, 131.7, 128.7, 123.5, 122.9, 121.1, 118.8, 110.8, 109.4, 105.8, 98.7, 79.3, 64.1, 63.5, 57.2, 37.6; MS (ES+) m/z 429.9 (M + 1). Example 32.2 1'-{[6-(Dimethylaminoidin-2-yl)methyl}-2,3-dihydrospiropyrano[2,3-g][l,4] Benzo Synthesis of Oxygenene-8,3'-吲哚]-2'(1Ή)-嗣 143924-sp-20091127-6 • 957- 201020257

Following the procedure as described in Example 32, and carrying out irrelevant changes, monomethylamine (40% w/w 'in water) was used to displace morphine and Γ [(6-chloropyridin-2-yl) was used. Methyl]·2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene -8,3'-+lo]-ΑΓΗ)-ketone-substituted 丨'- Your gas pyridine base) methyl]_2,3_dihydroindole snail [ruthenium [2,3-g][l,4] benzodioxanthene _8,3,_w哚]· 2,(1Ή)__, obtain 1·-{[6-(diamidoamine azaidine-2-yl)indolyl}_2,3_di-argon snail [吱,[2,3-g][l , 4] benzodioxanthene oxime]-2, (1Ή)-one (44%), as colorless solid: mp 196-197 ° C; 4 NMR (300 MHz, CDC13) &lt;5 7.45- 7.34 (m, 1H), 7.24-7.11 (m, 2H), 7.06-6.94 (m, 2H), 6.52-6.46 (m, 2H), 6.42-6.35 (m, 1H), 6.28 (s, 1H), 4.91 (ABq, J = 53.2, 15.3 Hz, 2H), 4.80 (ABq, J = 84.8, 9.1 Hz, 2H), 4.23-4.07 (m, 4H), 3.04 (s, 6H) ; 13 C NMR (300 MHz , CDC13) δ 177.4, 159.0, 155.3, 153.3, 144.5, 142.7, 138.2, 137.9, 132.2, 128.6, 123.5, φ 123.1, 121.2, 111.7, 109.9, 108.8, 104.5, 99.3, 80.3, 64.5, 63.9, 58.1, 46.0, 37.8; MS (ES+) m/z 430.0 (Μ + 1). Example 33 Γ-({6-[(diphenylmethylene)amino]ppyridin-2-yl}methyl)_2, 3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-83'-(4)哚]-2'(ΓΗ)-_ Synthesis-958· 143924- Sp-20091127-6 (S5 201020257

Let the chloro group p be biti-2-yl) fluorenyl]-2,3-dihydrospiro [bito-and-[2,3_g][i,4]benzodioxene-8,3'-吲哚]-2,(1Ή)-one (0.2 g, 〇.5 mmol) and the third _butanol sodium (0.06 g, 0.67 mmol) in 1,2-dimethoxy ethane (3 The mixture in milliliters® was degassed with argon for 15 minutes. Add (RH-)-l-[(S)-2-(dicyclohexylphosphino)dicyclopentadienyl]ethyldi-tert-butylphosphine (0.006 g, 〇〇1 mmol) ), palladium (II) acetate (0.01 g '0.05 mmol) and benzophenone imine (〇 1 ml, 0.6 mmol). The reaction mixture was stirred at 7 Torr for 24 h, then cooled to ambient temperature, diluted with di-methane (2 mL) and filtered over EtOAc. The pad was washed with di-methane (2 mL) and the filtrate was concentrated in vacuo. The residue was purified by column chromatography, and eluted with a gradient of 25% to 35% of ethyl acetate in hexane to give r_({6[(diphenylmethylene)amine). -yl}mercapto)-2,3-dihydrospich-[2,3_phantom [1,4]benzodioxanthene_8,3,_+wood]-2 (1 H )-嗣 (0.19 g '7〇%), as a colorless solid: MS (ES+) heart 565 8 (M+1). Example 33.1 Fluorine 2'-oxo snail [丨 并 & $ $ $ $ & & & & & $ $ $ ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? Synthesis of Biluo acid third vinegar 143924-sp-20O91127-6 •959- 201020257

In l'-(4-bromobenzyl)-5,6-difluorospiro[1-benzofuranium]-2,(1,H)-one (0.44 g '1.0 mmol) in anhydrous toluene ( Add (±)-(1,Γ-binaphthyl-2,2'-diyl)bis(diphenylphosphine) (0.093 g, 0.15 mmol) and (R)- to the solution in 1 mL) (+)-l-Boc-3-Aminotetrahydropyrrole (0.26 g, 1.4 mmol) followed by bis(diphenylmethyleneacetone)dipalladium (〇) (0.458 g, 0.1 mmol) With a third-butanol sodium (0.19 g '2.0 mmol). The reaction mixture was heated at reflux for 16 h then cooled to rt. The filtrate was concentrated in vacuo and the residue dissolved in ethyl acetate (100 mL). The mixture was washed with water (2×75 mL) EtOAc. The residue was purified by column chromatography and eluted with ethyl acetate in 20% to 40% gradient of hexane to give (3R)-3-({4-[(5,6-difluoroox) Spiro[1-benzofuran-3,3'-indole]-indole (2Ή)-yl)methyl]phenyl}amino)tetrahydropyrrole-1-carboxylic acid tert-butyl ester (0.403 g, 74%), ❹ brown oil: iHNMR (300 MHz, CDC13) 5 7.25-7.11 (m, 4H), 7.05-7.00 (m, 1H), 6.89 (d, J = 7.7 Hz, 1H), 6.78 (dd , J = 10.3, 6.3 Hz, 1H), 6.59 (s, 1H), 6.56 (s, 1H), 6.49 (dd, J = 7.9, 7.9 Hz, 1H), 5.02-4.93 (m, 2H), 4.74- 4.69 (m, 2H), 4.01 (br s, 1H), 3.76-3.68 (m, 2H), 3.46 (m, 2H), 3.20 (m, 1H), 2.21-2.12 (m, 1H), 1.87 (br s, 1H), 1.46 (s, 9H). Example 33.2 5,6-Difluoro-l'-{4-[(3R)-tetrahydropyrrol-3-ylamino]ylidene μ[1-benzofuran 143924-sp-20091127-6-960- (S) 201020257 -3,3'-吲哚]-2\1Ή) Synthesis of shoulder hydrochloride

* 2.3 HCI According to the procedure described in Example 11.111, and irrelevant changes were made using (3R)-3-({4-[(5,6-difluoro-2'-oxaspiro[1-benzo] Furan-3,3'-啕哚]-1'(2Ή)-yl)indolyl]phenyl}amino)tetrahydropyrrole-1-carboxylic acid tert-butyl ester replacement 4-[(5,6- Difluoro-2'-oxaspiro[1-benzofuran-3,3'-indole]-indole (2Ή)-yl)methyl]hexahydropyridine-1-carboxylic acid tert-butyl ester, obtained 5 ,6-difluoro-r-{4-[(3R)-tetrahydropyrrol-3-ylamino]]yl}spiro[1-benzofuran-3,3'-thirsty]-Τ(ΓΗ) - ketohydrochloride (78%), m.p.p.p.p.p.p.p.: 153 - 162 ° C; iH NMR (300 MHz, CDC13) 5 7.36-7.27 (m, 3H), 7.19 (d, J = 7.3 Hz, 1H ), 7.10 (d, J = 7.4 Hz, 1H), 7.06-6.97 (m, 3H), 6.92 (dd, J = 10.7, 6.4 Hz, 1H), 6.53 (dd, J = 8.4, 8.4 Hz, 1H) , 5.02-4.77 (m, 4H), 4.31 (s, 1H), 3.54-3.35 (m, 4H), 2.37 (s, 1H), 2.16 (s, 1H) ; 13 C NMR (75 MHz, CDC13) δ 178.6,158.4 (d, Jc. F = 10.7 Hz), 152.3 ❹ (dd, JC_F= 246.1, 12.8 Hz), 146.6 (dd, Jc-F= 239.5, 13.4 Hz), 143.3, 141.0, 133.4, 132.4, 130.5 , 130.4, 125.5 (d, Jc-F = 3.3 Hz), 125.0, 12 4.9, 120.2, 112.7 (d, JC.F = 20.3 Hz), 111.3, 100.8 (d, JC.F = 22.5 Hz), 82.1, 59.1, 57.7, 50.2, 46.3, 44.7, 30.4; MS (ES+) m/ z 448.2 (M + 1) 〇 to c2 6 H2 3 F2 N3 02 • 2.311 (:1 analytical calculation: (:, 58.77; 11, 4.80; condition 7.91. Found: C, 58.69; H, 4.37; N , 8.33. Example 33.3 Γ-[(5-moff-4-ylpyridin-2-yl)indenyl]-2,3-dihydrospich-[2,3-g][i,4 ]

143924-sp-20091127-6 -961- 201020257 Synthesis of stupo-oxodecene-8,3'-嘀哚]_2, (i,h)-ketone

According to the procedure as described in Example 33.1, and irrelevant changes were made, the (R)-(+)-; UBoc-3-aminotetrahydropyrrole was replaced with morpholine, and ubiquinone (10)-bromopyridine was used. 2-yl) fluorenyl]-2,3-di-argon snail [bite-and-[2,3_g][14] benzodioxanthene _8,3'- 哚 哚]·2,(ΓΗ)- Ketone substitution 1, -(4_bromomethyl)&gt;5,6-difluorospiro[1-benzofurfuran-3,3'-吲哚]-2'(1Ή)-_, obtained r_[( 5_?Foline porphyrin Pyridyl) methyl]-2,3-dihydrospiro[啥,[2,3-g][i,4]benzodioxene _8,3, _吲嗓]-2'(1Ή)-ketone (60%) ' is a pale yellow solid: melting point 2〇4-2〇6. (: ; 1 H NMR (300 MHz, CDC13) δ 8.23 (d, J = 2.4 Hz, 1H), 7.23-7.11 (m, 4H), 7.01 (dd, J = 7.5, 7.5 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 6.27 ( s, 1H), 5.13 (d, J = 15.3 Hz, 1H), 4.94 (d, J = 9.0 Hz, 1H), 4.89 (d, J = 15.6 Hz, 1H), 4.66 (d, J = 9.0 Hz, 1H), 4.21-4.11 (m, 4H), 3.87 (t, J = 4.8 Hz, 4H), 3.17 (t, J = 5.0 Hz,

4H) ; 13C NMR (75 MHz, CDC13) 5 177.4, 155.3, 146.3, 146.2, 144.6, ❺ 142.2, 138.3, 137.3, 132.2, 128.8, 123.7, 123.4, 123.2, 122.0, 121.1, 111.7, 109.7, 99.4, 80.2 , 66.6, 64.5, 63.9, 58.1, 48.5, 45.6; MS (ES+) m/z 472.2 (M + 1). Example 33.4 Γ-{[5-(dimethylamino)&gt;pyridin-2-yl]methyl}-2,3-dihydrospich-[2,3-g][l,4] benzene Synthesis of Dioxetine-8,3'-(4)哚]-Τ(1Ή)-one 143924-sp-20091127-6 - 962- (S; 201020257

Following the procedure as described in Example 33.1, and carrying out irrelevant changes, replace the (R)-(+)-l-Boc-3-aminotetrahydrop ratio with monomethylamine hydrochloride and use 1 '-[(5-Bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3$][1,4]benzodioxanthene-8,3 '-吲哚]-2'(1Ή)-ketone replacement 1,-(4-bromoindolyl)-5,6-difluorospiro[1-benzofuran-3,3W丨哚]-ΑΓΗ)- To obtain 1·-{[5-(dimethylamino)acridin-2-yl] fluorenyl}-2,3-dihydrospiro [bito-and-[2,3-g][l,4 Benzodioxanthene-8, Τ-ν丨哚丨哚]-2'(1Ή)-_ (23%), as a beige solid: mp 229-236 ° C; iHNMR (300 MHz, CDC13) δ 8.06 (d, J = 2.7 Hz, 1H), 7.22-6.92 (m, 6H), 6.50 (s, 1H), 6.27 (s, 1H), 5.11 (d, J = 15.3 Hz, 1H), 4.94 ( d, J = 9.0 Hz, 1H), 4.87 (d, J = 15.3 Hz, 1H), 4.65 (d, J = 8.7 Hz, 1H), 4.21-4.11 (m, 4H), 2.96 (s, 6H); 13 C NMR (75 MHz, CDC13) &lt;5 177.4, 155.3, 145.5, 144.5, 142.8, 142.4, 138.3, 134.1, 132.3, 128.8, 123.6, 123.2, 122.0, 121.2, 119.8, 111.7, 109.9, 99.3, 0 80.2 , 64.5, 63.9, 58.1, 45.7, 40.1 ; MS (ES+) m/z 430.1 (M + 1). Example 34 1·-[(6-Aminopyridin-2-yl)indolyl]-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxan Synthesis of octaene-8,3'-吲哚]-2'(1Ή)-_

1,-({6-[(diphenylarylene)amino group> than biting 2_yl}methyl)_2,3·dihydrospiro [bite 143924-SP-20091127-6 -963· 201020257 π南和[2,3-g][l,4]benzodioxanthene _8,3Ί 嗓]_2, (i'h)-ketone (0.18 g, 0.32 mmol) in tetrahydrofuran (1 A solution of 2M aqueous hydrochloric acid (0.5 ml) was added to the solution in EtOAc. The reaction mixture was stirred at ambient temperature for 1 min, cooled to 0 C and a saturated aqueous NaH.sub. The mixture was diluted with ethyl acetate (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2 EtOAc). The combined organic layers were washed with brine (45 mL) dried over anhydrous sodium sulfate and evaporated. The residue was purified by column chromatography and eluted with 65% ethyl acetate in hexane to give 1'-[(6-amino-acridin-2-yl)indolyl]-2,3- Hydrogen snail [biting and [2,34][1,4]benzoindoledioxene-8,3'-吲哚]-2'(1Ή)-_ (〇.1〇克, 76% ), as a colorless solid: mp. 240-241 ° C; 4 NMR (300 MHz, CDC13) 5 7.45-7.35 (m,1 Η), 7.25-7.14 (m, 2H), 7.06-6.98 (m, 1H), 6.91 -6.86 (m, 1H), 6.59-6.54 (m, 1H), 6.50 (s, 1H), 6.45-6.39 (m, 1H), 6.37 (s, 1H), 5.12-5.03 (m, 1H), 4.99 -4.92 (m, 1H), 4.80-4.63 (m, 4H), 4.25-4.05 (m, 4H); 13C NMR (300 MHz, CDC13) 5 177.5, 157.9, 155.2, 153.0, 144.6, 142.1, 139.0, 138.2 , 132.2, 128.8, 123.7, 123.4, 121.2, 111.7, 111.1, 109.6, 107.9, 99.3, 80.0, 64.5, 63.9, 58.1, 45.2; MS (ES+) m/z 401.9 (M + 1) » Example 35 Γ-[ (6-keto-1,6-dihydropyridin-3-yl)indolyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxan Synthesis of ene-8,3·-峋哚]-2'(1Ή)-ketone 143924-sp-20091127-6 - 964- (S) 201020257

^ [(Methoxypyridin-3-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxanthene m-dentone _克,0.58 mmol (), 〆, 化, (0.29 g '1.9 mmol) and water (2 drops) in acetonitrile () acetonitrile), stir the mixture, add gas-based trimethyl decane (0.23 ml) , L8 millimoles). The reaction mixture was stirred at ambient temperature for 16 hours. Further, sodium hydride (0.14 g, 0.95 mmol) and gas tridecyl decane (〇12 ml, 〇95 mmol) were added, and the reaction mixture was stirred at ambient temperature for 24 hours. Further, sodium iodide (0.29 g, i. 9 mmol) and chlorotridecyl decane (〇 23 ml, 1.8 mmol) were added, and the reaction mixture was stirred at ambient temperature for a day. A solution of sodium hydrogen sulfite (0.51 g, 4.9 mmol) in water (3 mL) and ethyl acetate (150 mL) was added. The layers were separated, and the organic layer was washed with brine (2········ The residue was triturated with diethyl ether, and the crude product was purified by preparative thin-layer chromatography and eluted with 30% of acetone in a methane to give ι'_[(6-keto-I,6-dihydrogen) Pyridin-3-yl)indenyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3'-吲哚]- 2,(1Ή)-ketone (0.15 g, 63%), as colorless solid: m.p. 249-250 〇C; !H NMR (300 MHz, CDC13) (5 7.61-7.46 (m, 2H), 7.31-7.21 ( m, 1H), 7.20-7.14 (m, 1H), 7.09-7.02 (m, 1H), 6.86-6.81 (m, 1H), 6.66-6.59 (m, 1H), 6.50 (s, 1H), 6.15 ( s, 1H), 4.92-4.60 (m, 4H), 4.24-4.06 (m, 4H); 143924-SD-20091127-6 -965- 201020257 13C NMR (75 MHz, CDC13) 5 177.7, 164.4, 155.2, 144.7 , 142.2, 141.4, 138.3, 133.5, 132.2, 129.0, 124.2, 123.8, 120.9, 120.7, 115.8, 111.4, 108.7, 99.5, 80.0, 64.5, 63.9, 58.0, 40.6; MS (ES+) m/z 403.0 (M + 1) Example 35.1 Γ-[(2-hydroxypyrimidin-5-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxan Terpene-8,3M丨哚]-ΑΓΗ), the synthesis

% Follow the procedure as described in Example 35, and perform an insignificant change using 14(2-methoxypyrimidin-5-yl)indenyl]-2,3-dihydrospiro[吱,[2, 3-g][l,4] benzodioxanthene-8,3'-吲哚]-2,(1Ή)-one substituted Γ-[(6-decylpyridin-3-yl)- ]]-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxene _8,3,_啕哚]-2'(1Ή)-one, obtained 14(2-hydroxypyrimidin-5(yl)indenyl]_2,3-dihydrospich-[2,3-g][l,4]benzodioxolene_8,3,_啕哚]-2,(1Ή)-one (19%), as a colorless solid: mp.25 (TC; iHNMR (300MHz, DMSO-d6) 5 8.31 (s, 2H), 7.37-7.28 (m, 1H ), 7.28-7.21 (m, 1H), 7.20-7.12 (m, 1H), 7.10-7.00 (m, 1H), 6.50 (s, 1H), 6.08 (s, 1H), 4.71 (s, 2H), 4.71 (ABq, J = 47.0, 9.4 Hz, 2H), 4.23-4.04 (m, 4H); 13C NMR (300 MHz, CDC13) δ 176.9, 154.7, 144.2, 141.7, 137.8, 131.9, 128.8, 123.7, 123.2, 121.2, 112.1, 111.0, 109.3, 98.8, 79.4, 64.2, 63.6, 57.2, 37.6; MS (ES+) m/z 403.9 (M + 1). Example 36 r-[(l-fluorenyl-6-fluorenyl- 1,6-dihydropyridin-3-yl)methyl]-2,3-dihydrospiro[cough And 143924-sp-20091127-6 -966- 201020257 [2,3-g][l,4]benzodioxanthene_8,3,·吲哚]_2,(1Ή)嗣

In 1-[(6-keto-l,6-dihydropyridin-3-yl)methyl]_2,3 dihydrospib-pyrano[2,3-g][l,4]benzoic Oxygen decene _8,3,_ρ5丨哚]_2, (1Ή) 嗣 (〇〇7 g, 〇17 mM φ mol) in anhydrous hydrazine, Ν 曱 曱 decylamine (3 ml) After cooling (〇.〇) solution, sodium hydride (60%, in mineral oil, 〇〇1 g, 〇25 mmol) was added. The mixture was stirred at ambient temperature for a few hours and methyl iodide (2 mL, 0.27 mmol) was added. The mixture was stirred at ambient temperature for 16 h, diluted with water (15 mL The combined organic layers were washed with brine <RTI ID=0.0> The residue was purified by column chromatography and eluted with a 10% to 30% gradient of acetone in dioxane to give a mercapto-6-keto-1,6-diox ratio. 3-yl)methyl]-2,3-dihydrospiro [flavor] Nanhe [2,3-g][i,4] benzodioxanthene-8, 吲哚]-2' (1Ή )-ketone (0.03 g, 42%) as colorless solid: m.p. 205-207 ° C; iHNMRGOO MHz 'CDCls) 5 7.40-7·34 (ιη, 2Η), 7.33-7.26 (m, 1H), 7.21-7.16 (m, 1H), 7.11-7.04 (m, 1H), 6.91-6.85 (m, 1H), 6.60-6.54 (m, 1H), 6.50 (s, 1H), 6.12 (s, 1H), 4.77 (ABq , J = 75.6, 9.0 Hz, 2H), 4.66 (ABq, J = 58.2, 15.3 Hz, 2H), 4.22-4.08 (m, 4H), 3.53 (s, 3H) ; 13 C 3SQVIR (75 MHz, CDC13) δ 177.7, 162.5, 155.2, 144.7, 141.5, 139.6, 138.3, 137.4, 132.2, 128.9, 124.3, 123.8, 121.3, 120.7, 114.0, 111.2, 108.5, 99.5, 143924-sp-20091127-6 -967- 201020257 79.8, 64.5, 63.9, 57.9, 40.8, 37.9; MS (ES+) m/z 416.9 (Μ + 1). Example 37 1-[(6-Aminopyridin-3-yl)indolyl]_2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanene-8, Synthesis of 3'-吲哚]_2, (i,h)-ketone

{5-[(2'-keto-2,3-dihydrospiro[吱,[2,3_g][14]benzodioxolene-8,3W|嗓]-1' (2Ή )-yl)methyl]P-pyridyl-2-yl)amino decanoic acid tert-butyl ester (1) 27 g, 0.53 mmol) cooled in anhydrous dioxane (12 ml) 1) suspended Add trifluoroacetic acid (4 ml) in the liquid. The mixture was stirred at ambient temperature for 3 hours' and concentrated in vacuo. The residue was dissolved in EtOAc (3 mL) (EtOAc m. Γ-[(6-Aminopyridin-3-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3'-啕哚]-2'(1Ή)-one (0.20 g, 93%), as a colorless solid: melting point 117-119 ° C; 1H NMR (300 MHz, DMSO-d6) 8.00-7.96 ( m, 1Η), 7.37-7.24 (m, 2H), 7.19-7.07 (m, 2H), 7.07-6.98 (m, 1H), 6.52 (s, 1H), 6.43-6.38 (m, 1H), 6.01- 5.96 (m, 3H), 4.82-4.62 (m, 4H), 4.21-4.07 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 176.6, 159.2, 154.6, 147.0, 144.1, 141.9, 137.7, 136.7, 131.7, 128.7, 123.5, 122.9, 121.2, 119.3, 110.7, 109.4, 108.0, 98.7, 79.2, 64.1, 63.5, 57.1; MS (ES+) m/z 401.9 (M + 1). Example 38 143924-sp-20091127-6 -968- 201020257 N: trans-N-{5-[(2'-keto-2,3-dihydrospiro[bit, s-[2,3_g][1, 4] Synthesis of benzodioxanthene -8,3'-θ丨哚]-Γ(2Ή)-yl) fluorenyl]p-pyridyl-2-yl) quinone imine carbenamide

/〇H

NS^_N on 14(6-Aminopyridin-3-yl)indolyl]_2,3-dihydrospiro[biting D-nan[2,3-g][l,4]benzene φ-dioxane Alkene, Ν-dimethylformamide, dimethyl hydrazine, dimethyl hydrazine, dimethyl hydrazine Alkal acetal (0 17 ml '1.3 mmol). The mixture was heated under reflux for 3 hours, allowed to cool to ambient temperature and additional hydrazine &lt;RTI ID=0.0&gt;&gt;&gt; The mixture was heated under reflux for 6 hours and allowed to cool to 50 °C. Hydroxylamine hydrochloride (0.15 g, 2.2 mmol) was added, and the mixture was stirred at 50 ° C for 16 hours. The mixture was allowed to cool to ambient temperature during which time the sinking system was deposited. The solid was transferred, washed with 2-propanol and Φ diethyl ether, and dried to give Ν'-hydroxy-N-{5-[(2,-keto-2,3-dihydrospiro[[ '3-g][l,4]benzodioxanthene-8,3'-啕哚]-1,(2Ή)-yl)methylcyclopyridin-2-yl}indenylene Amine (0.37 g, 82%) as colorless solid: m.p.: s.: s.: 232-232 〇 C; 1H NMR (300 MHz, DMSO-d6) 5 10.07 (s, 1H), 9.41-9.35 (m, 1H), 8,23-8.19 (m, 1H), 7.84-7.78 (m, 1H), 7.59-7.53 (m, 1H), 7.32-7.24 (m, 1H), 7.19-7.13 (m, 1H), 7.13-7.07 (m, 1H) , 7.07-6.99 (m, 2H), 6.52 (s, 1H), 6.05 (s, 1H), 4.86-4.83 (m, 2H), 4.73 (ABq, J = 44.3, 9.4 Hz, 2H), 4.22-4.06 (m, 4H) ; 13C NMR (75 MHz, DMSO-dg) 5 176.7, 154.6, 152.0, 146.6, 143924-sp-20091127-6 -969- 201020257 144.1, 141.8, 137.7, 137.5, 135.4, 131.7, 128.7, 124.0, 123.6, 123.0, 121.1, 110.8, 110.4, 109.4, 98.8, 79.3, 64.1, 63.5, 57.2; MS (ES+) m/z 444.9 (M + 1). Example 39 Γ-([1,2,4]Triazolo[l,5-a]pyridin-6-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][ l,4]benzodioxanthene _8,3,_♦ 朵]_2, (1Ή), the synthesis

Ν-Hydroxy-Ν-{5-[(2'-keto-2,3-dihydrospiro[吱,[2,3_g] to 4] benzodioxanthene-8,3' -呻哚]-1'(2Ή)-yl)methyl]acridine_2_yl}indolimamide (0.22 g, 0.5 mmol) cooled in tetrahydrofuran (7 mL) In the suspension (&gt;c), trifluoroacetic anhydride (8 ml, 〇54 mmol) was added slowly. The mixture was stirred at ambient temperature for 3 hours to sat. aq. Diluted and extracted with ethyl acetate (3 χ 5 mL). The combined organic layers were washed with brine (5 mL) and brine (5 mL). And concentrated in a vacuum. The residue was purified by column chromatography and eluted with ethyl acetate in 5% to 65% gradients of hexane to give Γ((1,2 4)triazolo[曱-)-2,3-dihydrospiro[吱吱[[] benzodioxanthene-like "bow" 2(1H)-one (0.11 g, 54%), as a colorless solid: Melting point 2〇7 2〇9t ; lfi NMR (300 MHz, DMSO-d6) δ 8.65 (s, 1H), 8.37 (s, 1H), 7.82-7.77 (m, 1H), 7.61 7.55 (m, 1H), 7.30-7.17 (m, 2H), 7.11-7.04 (m, 1H), 6.90-6.85 (m, 1H), 143924-sp-20091127-6 -970- 201020257 6.52 (s, 1H), 6.18 (s, 1H ), 5.03 (ABq, J = 40.9, 15.6 Hz, 2H), 4.80 (ABq, J = 79.6, 9.0 Hz, 2H), 4.23-4.09 (m, 4H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.7, 155.2, 154.2, 149.9, 144.8, 141.2, 138.4, 132.1, 129.8, 129.0, 127.0, 124.4, 124.0, 123.0, 120.5, 117.4, 111_4, 108.6, 99.5, 80.0, 64.5, 63.9, 58.0, 41.2; MS ( ES+) m/z 426.9 (M + 1). Example 40 r-[(2S)-2,3-Dihydroxypropyl]-2,3-dihydrospiro[c-c-[2,3-g][ Synthesis of l,4]benzodioxanthene-8,3'-indole (1Ή)-one

l'-{[(4S)-2,2-Dimethyl-indole, 3-dioxoindol-4-yl]methyl}-2,3-dihydrospiro[吱,[2,3 -g][l,4]benzodioxanthene _8,3,_w 哚]_2'(ι·Η)-one (0.66 g, 1.61 mmol) in glacial acetic acid (1 mL) The solution in water (5 ml) was stirred at ambient temperature for 18 hours' and concentrated in vacuo. The residue was recrystallized from ethyl acetate to give l,-[(2S)-2,3-dihydroxypropyl]-2,3-dioxaspiro[吱'[2'3-g][l '4] benzodioxanol · 8 3, _^ 哚] 2, (1 Ή) ketone (〇 59 g, 99%): melting point 179-181 ° C (ethyl acetate / hexane 1 η NMR ( 300 MHz, DMS0-d6) δ 7.30-7.25 (m, 1Η), 7.13-7.07 (m, 2H), 7.01-6.95 (m, 1H), 6.46 (s, 1H), 6.21-6.19 (m, 1H) , 5.02-4.94 (m, 1H), 4.71-4.57 (m, 3H), 4.14-4.06 (m, 4H), 3.81-3.54 (m, 3H), 3.39-3.32 (m, 2H) ; MS (ES+) m/z 369.9 (M + 1) 〇 Example 41 and Example 42 6-[(2'-Mercapto-2'3-dihydrospiro[2,3_§][1,4]benzoic Oxygen decene _8,3,_ 143924-sp-20091127-6 C. •971 - 201020257 啕哚]-Γ(2,Η)-yl)methylcyclopyridine_2-carbonitrile with 6_[(2 '· Keto 2,3 dihydrospiro[吱,[2,3-g][l,4]benzodioxanene·8,3%5丨哚]_Γ(2,Η) ) methyl ratio bite - 2-reaction of amine

Will be 14 (6-a gas-based bitten-2-yl) fluorenyl]-2,3-dihydrospiro[吱 并 砂 phantom] benzodioxanthene-8,3'-,?丨哚]-2'(1Ή)-ketone (0.50 g, 1.2 mmol), sodium (0.12 g '2.4 mmol) and nickel bromide (Π) trihydrate (〇〇26 g, I. a mixture of 1-methyl-2-tetrahydropyrrolidone (5 ml), heated under microwave irradiation at 200 ° C for 30 minutes, allowed to cool to ambient temperature and diluted with ethyl acetate. Wash with water and brine. The organic phase was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and dissolved in ethyl acetate/hexane (1/1) to give two products: the first compound to be dissolved was 6-[(2'-keto-2,3) - dihydrospiro[furo[2,3-lu][1,4]benzodioxanthene-8,3|-啕哚]-1, (2, ketone) fluorenyl] pyridine_2 - decyl nitrile (0.23 g '48%): refining point 213-215 ° C (ethyl acetate / hexane); 1 h NMR (300 MHz, DMSO-d6) δ 8.06-8.01 (m, 1 Η), 7.95-7.92 (m, 1H), 7.71-7.67 (m, 1H), 7.26-7.14 (m, 2H), 7.04-6.98 (m, 1H), 6.94-6.90 (m, 1H), 6.48 (s, 1H), 6.25 (s, 1H), 5.09 (ABq, 2H), 4.71 (ABq, 2H), 4.15-4.06 (m, 4H); MS (ES+) m/z 412.0 (M + 1). The second compound dissolved is 6-JX21- Brewed I-based-2,3-dihydrospiro [p-aramid 143924-sp-20091127-6 -972- 201020257 [2,3-g][l,4]benzodioxanthene _8,3,_吲哚]-1,(2Ή)-yl)methyl]pyridine-2-carboxamide (0.06 g, 12%): mp 113-115 ° C (ethyl acetate /hexane) ;1H NMR (300 MHz, DMSO-d6) δ 7.97-7.88 (m, 2 Η), 7.71-7.68 (m, 2H), 7.50-7.46 (m, 1H), 7.27-6.99 (m, 4H), 6.48 ( s, 1H), 6.12 (s, 1H), 5.06 (ABq, 2H), 4.79 (ABq , 2H), 4.15-4.06 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 177.2, 165.9, 155.4, 155.1, 144.6, 143.0, 139.3, 138.3, 132.0, 129.2, 124.5, 124.1, 121.6, 121.1, 111.6, 109.9, 99.2, 79.9, 64.6, 64.0, 57.7, 45.2; MS (ES+) m/z 430.0 (M + 1). Example 43 1^',6-Dihydroxy-144-methoxybenzyl)-2'-keto-1',2|-dihydrospiro[1-benzofuran-3,3'-啕哚] -5-Synthesis of imine amide

6-Carbo-indole-(4-methoxy-aryl)-2'-mercapto-indole, 2'-dihydrospiro[1-benzopyran-3,3'-啕哚]-5 - acetonitrile (0.84 g ' 2.10 mmol) and hydroxylamine hydrochloride (〇 2 g, 2,9 mmol) in ethanol (50 mL) in a stirred solution, adding triethylamine (0.40 ML '2.9 millimoles). The reaction mixture was stirred at reflux for 18 h and concentrated in vacuo. The residue was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and dried. The filtrate was concentrated in vacuo to give Ν',6-di-diyl-l,-(4-decyloxy)-2'-keto-oxime, 2'-dihydrospiro[1-benzo吱 -3-3,3'-啕嗓]-5-Residentimide-enamine (0.90 g, 99%): MS (ES+) m/z 431.9 (M+l). 143924-sp-20091127-6 -973 - 201020257 Example 44 3-Amino-indole-(4-methoxybenzyl) snail [indolobenzo-isoxazole _5,3,_ 吲哚]-2 ·(1Ή)-ketone synthesis

At 〇 ° C, in the oxime, 6-dihydroxy-1,-(4-decyloxybenzyl) 2,-keto-oxime, 2,-dioxaspiro[1-benzofuran-3, 3'-&lt;哚]-5- 醯 醯 imine amide (〇.9 〇, 2.1 mmol) involved in diphenylphosphine (0.71 g '2.7 mM) in tetrahydrofuran (3 〇 ml) In the solution, a solution of diethyl azodicarboxylate (〇·43 ml, 2.7 mmol) was added. The reaction mixture was allowed to warm to ambient temperature and stirred for 16 h. A 1% w/v aqueous solution of sodium hydroxide (10 ml) was added and the mixture was stirred for 3 hours. Most of the tetrahydrofuran was removed in vacuo and the resulting mixture was extracted with ethyl acetate (3 x 5 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography to give 3-amino-1,(4-methoxybenzyl)spiro[[,,,,,,,,,,, Oxazol-5,3'-indole]-2'(1Ή)-one (0.16 g, 19%): mp 214-216 〇C; !H NMR (300 MHz, DMSO-d6) δ Ί.29- 1.20 (m, 5Η), 7.14- 7.12 (m, 1H), 7.05 (s, 1H), 7.02-6.98 (m, 2H), 6.90-6.87 (m, 2H), 6.29 (s, 1H), 4.92- 4.69 (m, 4H), 3.69 (s, 3H) ; 13C NMR (75 MHz, DMSO-d6) δ 177.3, 162.8, 159.1, 155.3, 148.8, 142.6, 138.1, 132.5, 129.1, 128.7, 124.5, 124.1, 123.4 , 114.5, 109.9, 109.2, 93.0, 79.9, 57.9, 55.5, 42.9; MS (ES+) m/z 413.9 (M + 1). 143924-sp-20091127-6 -974- 201020257 Example 44.1 3-Amino-1'-7-pyridinyl-2-ylindolyl) snail [bito-benzo-isoxazole _5 3 吲哚]-2' ( 1Ή)-- Synthesis

6-Fluoro-2,-keto-1,-(pyridine-2-ylmethyl)-1,,2,-dihydrospiro tl_benzoxanthene ηNan_3,3L吲哚]-5- A mixture of carbonitrile (0.40 g, 2.7 mol) and acetonitrile hydroxamic acid (〇.6 g, 8.0 mmol) in N,N-dimethylformamide (20 mL) 'Add carbonated planer (2.60 g, 8.0 mmol). The reaction mixture was stirred at ambient temperature for 18 hours&apos; and water was added. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was purified by column chromatography eluting with ethyl acetate / hexane (2 / 3) + 0.1% v / v 7 N methanolic ammonia to give &lt;RTI ID=0.0&gt; 2-based fluorenyl) snail [bito-[3,2-f][l,2] benzisoxazole-5,3,-吲哚]-2'(1Ή)-one (0.05 g, 5 %): melting point 190-192 ° C (ethyl acetate / hexane); NMR (300 MHz, DMSO-d6) δ 8.54-8.52 (m, 1 Η), 7.79-7.73 (m, 1H),

7.35-7.20 (m,5H), 7.08-6.96 (m,3H), 6.15 (s,2H), 5.09-4.85 (m,4H); 13 C NMR (75 MHz, DMSO-d6) δ 177.2, 164.2, 163.3, 158.7, 155.6, 149.9, 143.5, 137.6, 131.7, 129.4, 126.4, 124.5, 123.6, 123.1, 121.9, 116.8, 111.5, 109.9, 91.4, 81.0, 56.8, 45.3; MS (ES+) m/z 384.9 (M + 1). Example 44.2 3-Amino-l'-[(2R)-tetrahydrofuran-2-ylindenyl]spiro[吱,[3,2-f][l,2]benziso-143924-sp-20091127-6 -975- 201020257 Synthesis of carbazole-5,3,?I哚]-2'(1Ή)-ketone

α) to 6-fluoro-2,-keto-l,-[(2R)_tetrahydrofuran-2-ylmethyl]-1,2,-dihydrospiro tl_benzofuran-3,3'-吲哚]-5-phthalonitrile (0.59 g, 1.6 mol) and C, (fat (〇% g, 4.8 mmol) in n,N-dimethylformamide (20 ml) Add the carbonic acid planer (1·56 g, 4.8 mmol) in the solution. The reaction mixture was stirred at ambient temperature for 19 hours, then heated at 60 ° C for 7 hours and allowed to cool to ambient temperature. The mixture was extracted with ethyl acetate (3×50 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and filtered and filtered. The filtrate was concentrated in vacuo. 30 ml), a mixture of water (1 ml) and concentrated hydrochloric acid (2 ml), and stirred under reflux for 4 h. The mixture was cooled to ambient temperature and neutralized with saturated aqueous sodium bicarbonate. The mixture was extracted with (3 X 1 mL). The combined organic extracts were washed with water and brine, dried over anhydrous sodium sulfate and filtered. The filtrate was subjected to column chromatography and eluted with (ethyl acetate/hexane (1/3) + 0.1% v/v 7N methanolic ammonia) to give 3-amino-1,-[( 2R),hydrofuran-2-ylindenyl]spiro[吱,[3,2-f][l,2]benzisoxazole-5,3,-吲哚]-2,(1Ή)- Ketone (0.37 g, 60%): melting point 116-119 ° C (ethyl acetate / hexane); iH NMR (300 MHz, CDC13) 5 7.35-7.32 (m,1H), 7.13-7.02 (m, 3H) , 6.09 (s, 1H), 6.84-6.81 (m, 1H), 4.91 (ABq, 2H), 4.31-4.25 (m, 1H), 4.13-4.09 (m, 2H), 3.86-3.66 (m, 4H) , 2.12-1.87 (m, 143924-SP-20091127-6 •976- 201020257 4H) ; (ES+) m/z 377.9 (Μ + 1) 〇Example 44.3 3-Amino-1 -[2-(difluoromethyl) Synthesis of snails [吱2[3 12_爪12] benzisoxazole·5,3'-吲哚]-2,(1Ή)-one

® According to the procedure described in Example 2, and with irrelevant changes, use 6-fluoro-2'-keto-oxime-[2-(trifluoromethyl)-based group H, 2i_ Dihydrospirobenzofuran-3,3'-indole-5-indenyl nitrile displaces 6-fluoroketone-1,-[(2R)-tetrahydrofuran-2-ylmethyl]-1',2 '-Dihydrospirobenzoquinone _3,3'-^丨嗓]_5-carbonitrile, obtaining 3-amino-indole-[2-(trifluoromethyl)-yl] snail [3,2_如,2]benzisoxazole-5,3,_&lt;哚]-2'(1Ή)-one (62%): melting point 262-264°C (ethyl acetate); iH NMR (300 MHz, DMSO-d6+ CDC13) δ 7.68-7.65 (m, 1Η), 7.56-7.51 (m, 1H), ^ 7.39-7.34 (m, 1H), 7.25 (s, 1H), 7.18-7.13 (m , 3H), 7.02-6.97 (m, 1H), 6.76 (s, 1H), 6.61-6.58 (m, 1H), 5.62 (s, 2H), 5.19-4.79 (m, 4H) ; MS (ES+) m /z 452.1 (M+ 1). Example 45 6-Carbo-2'-keto-l'-[(2R)-tetrahydrofuran-2-ylindenyl]-oxime, 2'-dihydrospiro[1_benzofuran-3, Synthesis of 3'-吲哚]-5-carbonitrile

143924-sp-20091127-6 -977· 201020257 Sodium nitrite (0.10) was added in small portions in a stirred solution of concentrated sulfuric acid (2.5 ml) in water (1.5 ml) at 〇 °C. Gram, 1 5 mmol, followed by hypophosphorous acid (0.50 mL, 4.6 mmol) with 3-amino-1L[(2R)-tetrahydrofuran-2-ylindenyl] snail [Blowing and [3 ,2-f][l,2]benzoxanthine wow-5,3% 嗓]-2'(1Ή)-ketone (0.17 g '0.45 mmol) in glacial acetic acid (2 ml) and ethanol ( Solution in 5 ml). The reaction mixture was stirred at 0&lt;0&gt;C for 6 h and then diluted with ethyl acetate &lt;~&gt; The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate/hexane (1/1) to give 6-hydroxy-21-keto-r-[(2R)-w-hydrofuran-2-ylindole. Base]-Γ, 2'-dihydrospiro[1-benzofuran_3,3,-β哚]-5-carbonitrile (0.09 g, 57%): m.p. 218-221 ° C (ethyl acetate / Hexane); 1 NMR (300 MHz, DMSO-d6) δ 11.27 (s, 1 Η), 132-1.21 (m, 1H), 7.19-7.14 (m, 2H), 7.03-6.98 (m, 1H), 6.86 (d, J = 6.0 Hz, 1H), 4.86-4.75 (m, 2H), 4.17-4.11 (m, 1H), 3.80-3.54 (m, 4H), 1.97-1.53 (m, 4H) ; 13C NMR ( 75 MHz, DMSO-d6) δ 176.8, 165.5, 163.2, 143.4, 131.6, 129.4, 128.1, 123.9, 122.4, 122.3, 117.4, 110.3, 98.1, 92.0, 81.0, 76.1, 67.6, 56.4, 29.1, 25.5; MS ( ES+) m/z 363.0 (M + 1). Example 45.1 6-Hydroxy-2·-keto-anthracene-[2-(trifluoromethyl decyl)-indole, 2'-dihydrospiro[1-benzofuran-3,3'-indole]- Synthesis of 5-carbonitrile

143924-SP-20091127-6 -978- 201020257 Following the procedure as described in Example 45, and applying irrelevant changes, 3-amino-1'-[2-(trifluoromethyl)-yl] snail was used. [Nitrate and [3,2-f][l,2]benzal 11th azole-5,3'-thirsty]-2'(1Ή)-ketone replacement 3-amino-r-[(2R )-tetrahydrofuran-2-ylmethyl]spiro[吱,[3,2-f][l,2]benzisoxazole-5,3W|哚]-2,(1Ή)-嗣, obtained 6 -hydroxy-2'-tho-l'-[2-(trifluoromethyl) aryl]_1,,2,_dihydrospiro[1-benzofuran-3,3|-吲哚]-5 - carbonitrile (38%): m.p. 122-124. (:(ethyl acetate); 1^^]^11 (300 MHz, DMSO-d6) (5 11.30 (s, 1H), 7.81-7.78 (m, 1H), 7.62-7.47 (m, 2H), 7.30 -7.23 (m, 3H), 7.18 (s, 1H), 7.08-7.03 (m, 1H), 6.73-6.70 (m, 1H), 6.53 ® (s, 1H), 5.11-4.83 (m^H) ; </ RTI> <RTIgt; 57.2, 41.0 ; MS (ES-) m/z 435.1 (M -1). Example 46 Γ-[2-(三气曱基)]基基]_ih-螺[吱,[3,2_刺azole_ 5,3,_&lt;哚]_2,(i,h)- Synthesis of ketone

6-Fluoro-2·-keto-142-(trifluoromethyl) yl]-Γ, 2,_dihydrospiro-benzopyran-3,3'-called noisy]-5-曱Nitrile (0.44 g, 1. 〇 mmol) in a stirred solution of &amp; dimethoxyethane (20 mL) was added hydrazine monohydrate (1 mL, 21 mmol). The reaction mixture was stirred under reflux for 9 hours and concentrated in vacuo. The residue was dissolved in ethanol (20 ml) and isoamyl nitrite (15 〇 143924-sp-20091127-6 -979. 201020257 ml ' 10.7 mmol), and sub-linic acid (2 〇 ml, Is millim). The reaction mixture was stirred at ambient temperature for 18 hr then EtOAc EtOAc (EtOAc) The combined organic extracts were dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo. The residue was subjected to column chromatography and eluted with ethyl acetate/hexane Q/i) to give Γ-[2-(trifluoromethyl)-yl]-1Η-spiro[吱,[3, 2-fHazole-5,3,-Θ丨哚]-2'(1Ή)-one (0.04 g '10%): m.p. 124-126. (:(ethyl acetate/hexane); !H NMR (300 MHz, DMSO-d6) δ 12.83 (s, 1 Η), 7.83-7.0 (m, 2H), 7.67- 7.63 (m, 1H), 7.54 7.49 (m,1H), 7.27-7.18 (m,4H),7.08-7.03 (m,1H), 6.95-10 6.94 (m, 1H), 6.81-6.77 (m, 1H), 5.07-4.83 (m, 4H) ; MS (ES-) m/z 436.2 (M -1). Example 46.1 Γ-0-pyridin-2-ylindenyl)-1Η-spiro[p-f-[3,2-f]carbazole -5,3,,哚]ketone

According to the procedure as described in Example 46, and with irrelevant changes, 6-fluoro-2,-keto-indole-(acridin-2-ylindenyl)-1,2,-dihydrogen was used. Snail benzopyrene-3,3'-θ| ]]-5-carbonitrile displaces 6-carbo-2'-keto-oxime-[2-(trifluoromethyl)-yl], 2_ The snail [1-benzo-bite-flavor-3,3'-p?丨嗓]-5-carbonitrile gives ι, _(ρ than bite_2_ylmethyl)-1Η-spiro[吱喃[3 ,2-f&gt;5 oxazole-5,3·-嘀哚]-2·(1Ή)-one (33%): mp 117-119 ° C (ethyl acetate / hexane); 4 NMR (300 MHz , CDC13) δ 10.21 143924-sp-20091127-6 _ 980 - (S; 201020257 (br s, 1H), 8.60-7.59 (m, 1H), 7.79 (s, 1H), 7.70-7.65 (m, 1H) , 7.31-6.89 (m, 7H), 5.24-4.77 (m, 4H); 13C NMR (75 MHz, CDC13) &lt;5 177.5, 160.7, 155.4, 149.6, 142.3, 141.7, 137.1, 134.9, 132.3, 129.0, 126.3, 123.7, 123.6, 122.8, 121.7, 119.1, 115.6, 109.7, 89.6, 80.6, 57.3, 46.1; MS (ES+) m/z 369.2 (M + 1). Example 46.2 1'-((3-(Trifluoro) Synthesis of methyl) acetophenone-2-yl)methyl)-1,6-dihydrospiro[吱,[3,2 ???-5,indoline]-2'-one

According to the procedure as described in Example 46, and with an insignificant change, 6-fluoroketone-1'-{[3-(trifluoromethylcyclopyridin-2-yl)indolyl}-oxime, 2·-Dihydrospiro[1-benzofuran-3,3'-诩哚]-5-carbonitrile displaces 6-fluoro-2·-keto-oxime-[2-(trifluoromethyl)benzyl ]-(2,3-dihydrospiro[1-benzofuran-3,3·-thirsty]-5-carbonitrile gives Γ-((3-(trifluoromethyl) acridine-2- Methyl)-1,6-dihydrospiro[Ombedo[3,2-fHazole-5,3'-dihydroindole]-2·-one (47%): mp 152-154° C (ethyl acetate / hexane); 1H NMR (300 MHz, DMSO-dg) δ 12.79 (br s, 1H), 8.80 (d, J = 6.0 Hz, 1H), 8.24-8.21 (m, 1H), 7.87 (s, 1H), 7.57-7.53 (m, 1H), 7.26-7.17 (m, 3H), 7.02-6.89 (m, 3H), 5.25 (ABq, 2H), 4.87 (ABq, 2H) ; 13C NMR (75 MHz, DMSO-dg) δ 172.5, 160.1, 153.2, 152.9, 143.5, 141.6, 135.5, 135.4, 134.1, 132.7, 129.1, 126.7, 124.0, 123.6, 123.2, 122.5, 119.1, 116.0, 109.5, 89.4, 80.0 , 56.9, 42.4; MS (ES+) m/z 436.9 (M + 1). 143924-sp-20091127-6 -981- 201020257 Biological Testing Various techniques are known in the art to test the hair The activity of a compound' or its solubility in a known pharmaceutically acceptable excipient. To make the invention described herein more fully understood, the following biological assays are proposed. It should be understood that this is The examples are for illustrative purposes only and are not to be construed as limiting the invention in any way. Biological Example 1 Influent Influx Detection (In Vitro Testing) This example illustrates in vitro testing for testing and profiling for stability. # Reagents for human or rat nanochannels in endogenous or recombinantly derived cells. This assay can also be used for % of Cannes channel blocking compounds. This assay is based on 胍 flux detection and is based on Reddy, nl, etc.

Wm. (1998), 41(17): 3298-302. The enthalpy influx was detected as a radiotracer flux assay to determine the ion flux activity of the sodium channel in a medium-microplate-based format. This assay utilizes 14C-hydrazine hydrochloride&apos; and uses various known nanochannel modulators to detect the efficacy of Formula 5 agents. Efficacy was measured by IC5Q calculations. The selectivity of the sputum is measured by comparing the efficacy of the compound to the channel of interest to us and its resistance to other sodium channels (also known as &quot;selective profiling. Each agent) is directed to cells that express channels of interest to us. The test is performed. The voltage-selected pass-through channel is either sensitive or insensitive. When evaluating the activity of a channel of interest to us, when it resides in a mixed cluster with other sodium channels, this property is Useful. Table 1 below is an excerpt from the cell line used to screen for the activity of certain channels in the presence or absence of 乂. 143924-sp-20091127-6 201020257 Table 1 Cell line mRNA performance functional characterization CHO- K1 (Chinese big cheek ovary; recommended host cell line) ATTC acceptance number CCL-61 • Nav1.4 performance has been confirmed by RT-PCR • No other Nav expressions were detected • On [14C] 胍 influx 18- to 20-fold increase, completely blocked with TTX (Nav 1.4 is a TTX-sensitive channel) L6 (White Rat Myoblast) ATTC number CRL-1458 • Performance of Nav 1.4 and 1.5 • at [14C]胍 inflow 10- to 15-fold increase, only partially blocked by sputum at 1〇〇nM (Nav1.5 is TTX resistant) SH-SY5Y (human neuroblastoma) ATTC number CRL-2266 • Published NaV1 .9 and Nav 1.7 performance (Blum et al.) • In the [14C] 胍 influx, 10 to 16-fold increase above background, partially blocked by TTX (Nav 1.9 is TTX resistant) (Human Neuroblast cell cell line 'ATCC number CRL-2268) ^---- • Performance of Nav 1.8 • Stimulation of BE2C cells with pyrethroids causes [14C] 胍 inflows 6 times higher than background Increased • TTX partial block influx (NaV1.8 is TTX resistance) PC12 (large white sputum cell tumor) ATTC number CRL-1721 '---- • Performance of Nav 1.2 • Inflow in [14C] 8- to 12-fold increase in amount, completely blocked by TTX (Nav 1.2 is a TTX-sensitive channel) ® Recombinant cells expressing these sodium channels can also be used.

Breeding and genus are known to those skilled in the art (see, for example, Klugbauer, N et al., 乂 (1995), 14(6): 1084-90; and Lossin, C. et al., (2002), 34, 877_884 page). Cells that express the channels of interest to us are grown according to the supplier, or in the presence of recombinant growth, ', cell culture, in a selective growth medium such as G418 (Gibco/Invitrogen). The cells were separated from the culture dish with an enzyme solution (IX) trypsin/EDTA (Gibco/InVltrC&gt; gen), and density and viability were analyzed using a hemocytometer (Neubauer). The isolated cells were washed and resuspended in their medium, 143924-sp-20091127-6 -983-201020257 and then covered in a scintillation plate (Beckman Coulter) (approximately 100,000 cells/well)' Incubate at 37 ° C / 5% C02 for 20-24 hours. In low sodium HEPES-buffered saline solution (LNHBSS) (150 mM gas choline, 20 nM HEPES (Sigma), 1 mM gasification, 5 mM gasification If, 1 mM gasification town, 10 mM glucose) After extensive washing, the drug diluted with LNHBSS is added to each well (different concentrations of reagents can be used). The activation/radioactive labeling mixture contains aconitin (Sigma) to increase the percentage of time the sodium channel is opened, and 14C-indole hydrochloride (ARC) to measure the flux through the voltage-gated sodium channel. After mixing the cells with the activation/radioactive labeling mixture, the scintillation plates are incubated at ambient temperature. After the incubation, the scintillation plates were extensively washed with LNHBSS supplemented with Sigma. The scintillation plates were allowed to dry and then counted using a Wallac MicroBeta Trilux (Perkin-Elmer Life Sciences). The ability of the agent to block sodium channel activity is measured by comparing the amount of 14C-stroke present in cells that exhibit different sodium channels. Based on this data, various calculated values, as detailed elsewhere in this patent specification, can be used to determine if a reagent is selective for a particular sodium channel. The IC5 enthalpy of the reagent for a particular sodium channel can be determined using the general methods described above. IC5〇 can be measured in two replicates or three replicates using a 3, 8, 10, 12 or 16-point curve with an initial concentration of 1, 5 or 10, continuously to achieve sub-nanomol concentration, The final concentration of the micromolar concentration and the low micromolar concentration range is diluted. Typically, the point concentration of the reagent is set at 1 _, while the continuous concentration of the semi-dilution solution is applied (eg, 0.5 5 and 0.25 /zM; 10 /iM and 0.125 _; 20 //Μ, etc.). The IC50 curve is calculated using the 4-parameter calculation mode or the sigmoidal dose-response mode (integral = (A+((BA)/ 143924-SP-20091127-6 •984- 201020257 (l+((C/x,D)))) a multiple of selectivity, a factor of selectivity, or a multiple of selectivity, calculated by subtracting the value of the sodium channel by the reference nanochannel, for example, 15, and a representative compound of the present invention, when used in the above assay When the known cell line exhibiting the nanochannel is tested, it shows the ic50 (_active content) as shown in Table 2 below, where "A" refers to the IQ〇 activity content from i to (10), and "B&quot; IC5. The active content ranges from (10) nM to ιm, "c&quot; refers to the heart 〇 activity content from i - to 10_, and "D" refers to &amp; the active content is equal to or greater than 10. The example numbers provided in Table 2 Corresponding to the examples in this article: Table 2

Example No. Compound name IC5〇1 2-methylspiro[c-buto[2,3-f][l,3]benzoxazole_7,3,_,5丨嗓]_ 2'(1Ή)- Ketone C 1.1 1 -L(6-methylρ ratio η定_2_yl)methyl]_2,3·dihydrospiro j&gt; Furano[2,3-g][l,4]benzoic Oxygen ore _8,3,-吲哚]-2'(1Ή)-ketone A 1.2 1'-(pyridin-3-ylindenyl)-2,3-dihydrospiro[furo[2,3 -g][l,4] Benzodioxanthene -8,3'-»?丨哚]-2·(1Ή)-ketone A 1.3 Γ-{[2,5-Dimethyl-1- (1-methylethyl)-indole-pyrrol-3-yl]methyl} snail [吱,[2,3-f][l,3]benzodioxol-7,3'-丨哚]-2Χ1Ή)-ketone A 1.4 5-(benzyloxy)-indole-[(5-chloro-2-indenyl)methyl]spiro[1-benzofuran-3,3'-哚]-2'(1Ή)-ketone C 1.5 7'-Bromo-based spiro[吱,[2,3-f][l,3]benzodioxol-7,3'-啕哚] -2'(1Ή)-ketone A 143924-sp-20091127-6 •985- 201020257

Example No. Compound name ICS0 1.6 14(3-Isoiso-) sitting -5-yl)methyl]spiro[吱,[2,3-f] [1,3]benzodioxanthene- 7,3·-蚓哚]-2'(1Ή)-ketone A 1.7 Γ-[(4-bromo-2-ylphenyl)indolyl] snail [吱,[2,3-f][l , 3] benzodioxanthene-7,3'-吲哚]-2'(ΓΗ)-ketone A 1.9 Γ-{[2-methyl-5-(trifluoromethyl)-1,3 -oxazol-4-yl]methyl} snail [吱,[2,3-f][l,3]benzodioxolene-7,3'-吲哚]-2'(1Ή) -ketone A 1.10 (3R)-5,6-«-a nitrogen snail [本和[l,2-b · 5,4-b*]二咬哚哚··2'(1Ή)-ketone C 1.10 (3S -5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3,-W 哚]-2'(ΓΗ)-ketone A 1.11 (R) -3,7-dihydro-2Η-spiro[benzopyrano[5,6-b][l,4]dioxanthracene-8,3*-diazepine]-2*-嗣C 1.11-2,3-Dihydrospiro[吱,[2,3^][1,4]benzodioxanthene, -8,3'-吲哚]-2,(1Ή)-one A 1.12 (8S)-l'-{[3-(Trifluoromethyl)ρ-pyridin-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene-8,3·-呻哚]-2'(1Ή)-ketone A 1.13 (8S)-r-[(5-hydroxypyridin-2-yl)methyl] -2,3- Hydrogen snail [[,,,,,,,,,,,,,,,漠基pyridine-2-yl)indenyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2,(1Ή)-ketone A 1.15 Γ-{[5-(4-chlorophenyl)-2-(tri-f-methyl)pyran-3-yl]fluorenyl} snail [bite 11 Nanhe [ 2,3-f][l,3]benzodioxolene-7,3'-υ 哚]-Τ(ΓΗ)-ketone C 1.16 1 -{[5-lacyl-1-methyl -3-(trifluoromethyl)-1Η-ρ ratio. -4-yl]methyl}spiro[吱,[2,3-f][l,3]benzodioxene _7 3L 啕哚]-2·(1Ή)-ketone' A 1.17 Γ-(5-decyloxyphyllotoxin-3-yl) snail [吱,[2,3-f][l,3]benzodioxanthene-7,3·-吲哚]- 2'(1Ή)-ketone' B 143924-sp-20091127-6 -986- 201020257

Example No. Compound name IC5〇2.3 Γ-(Diphenylmethyl)-5,6-dimercaptospiro[1-benzofuran_3,3'_吲哚]-2'(ΓΗ)-ketone C 2.6 A Oxybenzyl)-3-methylspiro[吱,[3,2-f][l,2] benzisoxazole-5,3'-throindole]-2'(1Ή)-one A 2.9 Γ-(Diphenylmethyl)-5-fluorospiro[1-benzofuran_3,3'_吲哚]-2,(1Ή)-one C 2.11 14-diphenylmethyl)-2,3 - Dihydrospiro[啥,[2,3-g][l,4]benzodioxanthene, -8,3'-W, stagnation, -2'(1Ή)-ketone C 2.14 Γ-( Diphenylmethyl)-2-methyl snail [bito-and-[2,3-f][l,3]benzoxazole-7,3·-,?丨哚]-2,(1Ή)-one D 2.16 Γ-(diphenylmethyl)-3-methylspiro[吱,[2,3-f][l,3]benzoxazole-7,3'-啕哚]-2,2, (1,11,311)-dione D 2.22 6-Bromo-1·-((5-(trifluoromethyl)pyran-2-yl)methyl pH-spiro [benzofuran-3,3 '-Dihydroanthracene-2'-keto C 2.23 5-Bromo-indole-((5-(trifluoromethyl)methane-2-yl)methyl)-2H-spiro[benzofuran- 3,3'-dihydroanthracene-2'-one B 2.24 6'-Isoamyl-3,7-dihydro-2H-spiro[benzofuro[5,6-b][l,4 Dioxerem-8,8'-pyrazolo[5,4&lt;]^丨哚]-7'(6Ή)-ketone A 2.25 6- ((5-(Trifluoromethyl)pyran-2-yl)indolyl)-2,3,5,6,-tetrahydro-2-indole-spiro[[1,4]dioxene terpene [ 2,3-fH哚-8,3'-benzofuro[6,5-b]furan]-7(6H)-one B 2.26 6-((())-tetrahydrofuran-2-yl)methyl -2,3,5,6,-tetrahydro-2'11-spiro[[1,4]dioxolyseno[2,3-f]indole-8J-benzofuran[6 ,5-7]furan]-7(6H)-嗣C 2.27 6-((5-(trifluoromethyl-anthran-2-yl)indolyl)-2,3,3,,7,-tetrahydro -2Ή-spiro[[1,4]dioxoindrene[2,3&lt;]啕哚-8,8'-benzofuro[5,6-b][l,4]dioxan Alkene-7(6H)-one B 2.28 1-decyl-indole-{[5-(^fluoroindolyl)pyran-2-yl]methyl}-2,3-dihydro-1Η-spiro [吱 并[3,2-g][l,4]benzoindole-8,3,- 哚 哚]-2'(ΓΗ&gt;-keto hydrochloride B 143924-sp-20091127-6 •987- 201020257

Example No. Compound name IC5〇2.29 1-Methyl-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-2,3-dihydro-1H-spiro[吱,[3,2-g] [l,4] Stupid and cultivating -8,3·-啕哚]-2'(1Ή)-_hydrochloride B 2.30 4-mercapto-14(2R)-tetrahydrofuran-2-yl group ]]-3,4-dihydro-2Η-spiro[吱,[2,3-g][l,4]benzoindole-8,3'-"5丨哚]-2'(1Ή) -keto C 2.31 r-[(2R)-rahydrofuran-2-ylmethyl]-4Η-spiro [bito-and-[3,2-g] [1,3]benzodioxanthene_6 ,3·-啕哚]-2'(1Ή)-ketone C 2.34 2,2-digas-1'-{[5-(trifluoromethyl)pyran-2-yl]methyl} snail [bite喃[2,3-f][l,3]benzodioxol-7,3,-啕哚]-2'(ΓΗ)-keto B 2.35 2,2-difluoro-1'- {[5-(Trifluoromethyl)pyran-2-yl]methyl}spiro[吱,[2,3-f][l,3]benzodioxene_7,3,_吲哚]-2'(ΓΗ)-ketone C 2.36 2,2-difluoro-14[3-(trifluoromethyl)acridin-2-yl]indenyl} snail [吱和[2,3- f][l,3]benzodioxanthene _7,3,-ρ 哚]-2'(1Ή)-ketone C 2.38 3Κ4-methoxybenzyl)-5,6-dihydrospiro [Benzo[i,2-b : 5,4-b,] difuran-3, fluorenyl-pyrrolo[3,2-f]quinoline]-2,(3Ή)-one B 2.39 6-hydroxy- Γ-(4-methoxyindenyl)_2, keto-yl 2,-dihydrospiro[μ benzofuran-3,3'-吲哚]-5-indolecarbonitrile C 2.40 6-fluoro- , 1'-(4-methoxyindenyl)_2'-mercapto-indole, 2,_dihydrospiro[μ benzopyran-3,3'-noise]-5-carbonitrile C 2.41 1 '-(4_Methoxy-benzyl)-3-methylspiro[吱和苯苯并呤-7,3·-吲哚]-2, (1, HV ketone C 2.44 1'-(two Stupid H'-fluoro 2,3-dihydrospiro[吱,[2,3-g][1,4]benzodioxanthene_8,3,_吲哚〗 _2, (1Ή)ketone B 2.45 Γ-(4-fluorophenyl)-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene -8,3·- Noisy]_2,(1Ή)-ketone A 2.49 &gt; 演基-1'10 bis-2-ylmethyl)_2,3_dihydrospiro[吱'[2'3-g][l, 4] benzodioxanthene _8,3·_ρ?卜朵]_ 2,(1Ή)-ketone A 143924-sp-20091127-6 •988-

201020257

Example No. Compound name ICso 2.50 2-mercapto-l'-(p is determined to be _2_ylmethyl)-ΐ',2,2·,3-tetrahydrospiro[pf-f-[2,3- g][l,4]benzodioxanthene_8,3,-吲哚]-5,-carbonitrile A 2.61 Γ-(diphenylfluorenyl)-5,6-difluorospiro[1- Benzofuran_3,3,-p-bend]-2\1Ή)-ketone D 2.63 4,5-dimethoxy-indole-{[5-(tri-methyl)pyran-2-yl ]曱基}-2,3-Dihydrospiroindole[2,3-g][l,4]benzodioxanthene-8,3·-啕哚]-2'(1Ή) -嗣B 2.64 4',7^曱oxy-142-(2-methoxyethoxy)ethyl]_2,3_dihydrospiro [bite and [2,3-g][l,4 Benzodioxanthene-8,3'-啕哚]-2·(1Ή)-keto B 2.65 6-[2_(2-methoxyethoxy)ethyl]-2,2,, 3,3,-tetrahydrospiro[1,4-dioxolynene[2,3-fl吲哚-8,8--furo[2,3-g][l,4]benzoic Oxygen decene]_7(6Η)-鲷C 2.66 Μ4-methoxybenzyl)_2,3-dihydrospiro[吱,[2,3-g][l,4]benzo-oxygen Rare -8,8'-[l,3]p plug" and [5,4-e]i丨嗓]-7·(6Ή)-keto B 3 6-methoxy-5-fluorenyl snail [ 1-benzofuran_3,3,_吲哚]_ 2,(1Ή)-ketone C 3.1 4·-Chloro-5,6-dihydrospiro[Benzene [i,2-b : 5,4-b,]difuran-3,3'-吲哚]-2'(1Ή)-嗣A 3.2 6-Moly snail [1-benzofuran_3,3 ,_吲哚]_2,(1印_ketone C 3.3 5'6-dimethylspiro[μbenzofuran_3,3,_令朵]_2'(ι,η)-ketone B 3.4 5'- Gas-based-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3,-吲哚]-2'(1Ή)-ketone~- C 3.5氟 Fluoro-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3^吲哚]-2·(1Ή)-ketone C 3.6 &gt; τ 螺 吱 [吱 苯 benzoisoxazole _53, 啕哚 啕哚]-2' (1 Ή)-ketone B 3.7 &gt; fluoroyl-6-methoxy snail [μbenzofuran _3, 3L 吲哚]_ 2,(1Ή)-ketone C 143924-sp-20091127-6 201020257

Example No. Compound name IC5〇3.8 5-Fluoro-spiro[1-benzofuran-3,3'-啕哚]-2·(1Ή)-keto C 3.10 2,3-Dihydrospiro[吱喃和[2 ,3-g][l,4]benzodioxanthene -8,3'-吲哚]-2'(1Ή)-ketone A 3.11 3,4-dihydro-2Η-spiro [2,3-h][l,5] stupid and dioxonia heptaene-9,3'-吲哚]-2^1 ugly)-keto C 3.12 2-mercapto snail [吱 并 [2 ,3-f][l,3]benzoxazole-7,3'-吲哚]-2,(1Ή)-ketone D 3.13 3-mercaptospiro[吱,[2,3-f][ l,3]benzoxazole-7,3,-啕哚]-2,2'(1Ή,3Η)-dione C 3.14 1-methylspiro[吱,[3,2-f][l , 3] benzoxazole _7,3,-吲哚]-2,2'(1Η,1Ή)-dione C 3.15 7'-gas-based-5,6-dihydrospiro[benzo[i, 2-b: 5,4-b']bi-chewing-3 3'-呻哚]-2'(1Ή)-ketone' B 3.16 7'-fluoro-5,6-dihydrospiro[benzo[ 1,2 7:5,4,7,]difuran-3 3'-啕哚]-2\1Ή)-keto B 3.17 4'-Fluoro-7'-methyl-5,6-dihydrospiro [ Benzo[ub:5,4-b]difuran-3,3'-吲哚]-2'(1Ή)-keto B 3.21 6,7-dihydro-5Η-spiro[唉,[3,2 -g]decene_3,3,-&lt; 哚]_ 2-(1Ή)_ ketone B 3.22 1_曱基_1Η_ΡΡ夫和[3,2-g][l,4]benzene And ploughing -8,3 -&lt; 哚]-2,2'(1Ή,3Η)-dione C 3.23 4-decyl f,7-dihydrospiro[benzofuran[5 6_b][14p No.8,3'- Dihydroanthracene;]·2,,3(2Η)-dione C 3.24 2,3'6,7-tetrahydrospiro[吱,[3,2_g] olefins_5 3,·ρ5丨哚] _ 2,(1Ή)-ketone C 3.25 (3S)-6-methoxy-5-methylspiro tl•benzofuran_3,3,啕哚]_ 2'(1Ή)-ketone C 3.26 (3RUuf Base_5_methylspiro[1_benzopyran-3,3,5丨嗓]_ 2 (1 H)-keto C 3.28 2',3',5,6_f spiro[benzo[Ub: 5 ,4,7,]difuran-3,8,-[1,4]-oxo-area[2,3-fH哚]-7,(6Ή)-ketone C 143924-SD-20091127-6 201020257 ❿

Example No. Compound name ic5〇~~ C 3.29 6-methoxyketo-I',2,-dihydrospiro-benzofuran_3 3·^厂哚]-5-carbonitrile 3.30 6-fluoro- 2-keto-anthracene, 2'-dihydrospiro[ι_benzopyrano_3,3,_吲哚]-5-indolecarbonitrile C 3.32 4·-bromo-2,3-hydrogen snail [ Bite and [2,3_g][1,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-嗣B 3.33 4·-Fluoro-2,3-- Hydrogen snail [Ρ夫喃[2 3 瓜4]benzodioxene-8,3'-吲哚]_2' (1,Η&gt; ketone A 3.34 4'- porphyrin-3-yl-2, 3-dihydrospiro[Miso[2,3_g][1,4]benzodioxanthene-8,3'-吲嗓]-2'(1Ή)-keto B 3.35 4'-(4 ·, Oxygen hand phenyl ^ 2,3 - dihydrospirobinated OgD, 4] benzodiazepine woman -8, 3 '- noisy noise - 2, (1 Ή) - ketone B 3.40 snail [ ♦Duo-3,3·-Soul-[2,3-]]benzofuran]_2(1Η)__ ^ 5,5'-dioxide C 3.41 snail [吱β南和[3,2-e ][2,l,3] Stupid and ρ No.2 _8 3'-ρ5 Budu 1- 2,(1Ή)-ketone' C 3.42 6-Gas-2,3-dihydrospiro [3 2_叩4]benzodioxanthene-9,3'-W 哚]-2,(1,Η)-ketone C 3.44 'monofluorospiro[1-benzo-p-pentan_3, 3,-ρ5丨嗓1-2, (TH V ketone C 3.45 3.46 5,ό'/,8'-tetrahydrospiroindole 哚-3,3,-naphtho[2,3-b]furan]-2(1H)-ketofuran_3,3,_吲嗓1: a 2 (1 Η)-keto CC 3.47 ethoxy group) snail [1_benzopyrano_3,3,-吲哚]-2(1Ή)-ketone C 3.48, Bufu methane [2,3 £][1,4]benzodioxanthene~7,3-qiao哚]_2,(ι,η)-ketone C 3.49 z'y $,[cough and [[illusion] Benzodioxanthene-di-Jl,3]carbazolo[5,4-φ5-dra]_7,(6Ή&gt;ketone C 3.50 4,〇-二Ζ敦基-2,3-dihydrospiro [sniffing [2,3_g][1,4]benzo-_11^1^ decene-8,3·-吲哚]-2·(1,Η)-ketone C 143924-sp-20091127-6 -991 - 201020257

Example No. Compound name IC5〇3.51 snail [bito-and-[2,3-g]porphyrin-8,3,-吲哚]-2,(1Ή)-ketone c 4 1 _(tetrahydro-2Η- shout喃-2-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚]-2, (1, 11)-ketone A 4.2 1 -[(2-Alkyl-1-methyl-1H-imidazol-5-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b: 5 ,4-b,]difuran-3,3,-吲哚]-2.(1Ή)-ketone A 4.3 1 -[(2R),hydrofuran-2-ylmethyl]_5,6-dihydrospiro [Benzo[l,2-b:5,47']difuran-3,3,-anthracene-2,(1Ή)-one A 4.4 methylbutyl)-5,6-dihydrospiro [Benzo[l,2-b: 5,4-7,]di-n--3,3'-啕哚]-2'(1Ή)-ketone A 4.5 1'-[(25)-tetrahydrofuran_2- Methyl]-5,6-dihydrospiro[benzo-~[1,2-7:5,4-7]difuran-3,3,-吲哚]-2,(1Ή)-ketone A 4.6 Γ-(tetrahydro-2-indole-piperazin-4-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3'-吲哚;μ2,(1Ή)-keto B 4.7 5-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4h']difuran-3, 3'-吲哚]-Γ(2Ή)-yl)methyl]pyran-2-carboxylic acid methyl ester A 4.8 1'-(1,4-dioxolan-2-yl-methyl 5&gt;5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3·-吲哚]-2,(1Ή)-ketone A 4.9 1' -{[1-methyl-3-(trifluoromethyl)-111-峨 -4-yl] fluorenyl}-5,6-a snail [benzo[i,2-b: 5,4 -b'] two bites β South-3 3'-port 5丨哚]-2'(1Ή)-ketone' B 4.10 Γ-(tetrahydro-2Η-»派喃-3-ylindenyl)_5,6 - dihydrospiro[{,2-b:5,4-bf]dioxan-3,3·-呻哚]-2,(1Ή)-keto A 4.11 2-[(2'-ketone) Base-5,6-di-argon[benzo[i,2-b : 5,4-b,]difuran-3,3'-吲哚]-1,(2Ή)-yl)methyl]_1 , 3_carbazole-4-carboxylic acid methyl ester A 4.12 Γ-(2-fluoroindolyl)-5,6-dihydrospiro[benzo[i,2-b: 5,4-b']·^ · ρ夫喃-3,3,-吲哚]-2'(1Ή)-ketone A 4.13 1·-(4-fluoroindolyl)-5,6-dihydrospiro [benzo[1,2 seven: 5,4-b,]difuran-3,3'-吲哚 A

143924-sp-20091127-6 •992·

(S 201020257

Example number Compound name IC5〇4.14 1&quot;&quot;卞基-5,6-—Wind snail [本和[1,2七:5,4-b']二咬喃-3 3'·吲哚]ketone' A 4.15 Γ-(biphenyl-4-ylmethyl)-5,6-dihydrospiro[benzoHb: 5,4-b'] difuran-3,3W丨哚]-2'(1Ή)- Ketone A 4.16 1'-(tetrahydrofuran-3-ylindenyl)-5,6-dihydrospiro[benzo[i,2-b : 5,4-b']di-n--3,3'-吲嗓]-2'(1Ή)-keto B 4.17 Γ·[(3-bromoisoxazol-5-yl)methyl]_5,6-dihydrospiro[benzo[l,2-b: 5, 4-b']dipyran-3,3'-mouth?丨嗓]-2'(1Ή)-ketone A 4.18 14(5-bromofuran-2-yl)indolyl]-5,6-di Argon snail [benzo[l,2-b:5,4-b']dioxime&gt;South_3,3'_U5丨哚]_2'(1Ή)·ketone A 4.20 1'-(propylene oxide -2-ylmethyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,anthracene-2'(1Ή)-one B 4.21 Ethyl-1 Η-imidazol-5-yl)methyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxin-3,3^5 ]-2'(1Ή)-keto B 4.22 3-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-b,]difuran-3,3f -吲哚]-Γ(2Ή)-yl) fluorenyl]benzonitrile A 4.23 4-((2'-keto-5,6-dihydro-2Η-spiro[benzo喃[6,5-7]Cough-3,3'-dihydro W哚]-Γ-yl)methyl)benzonitrile A 4.24 4'-[(2·-keto-5,6-di Hydrogen snail [benzo[l,2-b:5,4-b,]difuran-3,3'-吲哚Η·(2Ή)-yl)methyl]biphenyl-2-carbonitrile B 4.25 L'-{(2S)-2-[()oxy)methoxy]propyl 5-,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran- 3,3'-W 哚]-2'(1Ή)-keto B 4.26 1'-(2,3-dihydro-1,4-benzodioxanthene-6-ylindenyl)-5, 6-Dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3W丨哚]-2'(1Ή)-ketone A 4.27 Γ-(2,1,3- Benzooxadiazol-5-ylindenyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxin-3,3'-qiao哚]- 2,(1Ή)-ketone A 4.28 Γ-(2,1,3-benzoxazol-5-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b: 5, 4-b']difuran-3,3·-吲哚]-2·(1Ή)-ketone A 4.29 benzylnorfosin-2-yl)methyl]-5,6-dihydrospiro[benzo [l,2-b : 5,4-b']difuran-3,3'-吲哚]-2·(1Ή)-ketone C 143924-sp-20091127-6 -993· 201020257

Example No. Compound name IC5〇4.33 4-Alkyl-indole-{[5-(Trifluoromethyl)pyran-2-yl]methyl}-5,6-diaza snail [本乙[l,2- b · 5,4-b'] two bites. South-3,3^5丨嗓]_ 2,(1Ή)-ketone A 4.34 4'-Chloro-l'-[(2R)-rahydrofuran-2-ylindenyl]-5,6-di Hydrogen snail [benzo[l,2-b: 5,4-b·] 吱 -3-3,3'-,5 丨 mouth]-2'(1Ή)-_ A 4.35 4'-bromo-1 '-[(211)-Tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-啕哚]-2'(1Ή)-ketone A 4.36 l'-(3-mercaptobutyl)-2,3-dihydrospiro[Octa[2,3-g][l,4]benzo-oxo陆园稀-8,3'-巧丨p朵]-2'(1Ή)-嗣A 4.37 Γ-(tetrahydro-2Η-l-pyran-4-ylindenyl)-2,3-dihydrospiro [ Miso-[2,3-g][l,4]benzodioxanthene_8,3,-mouth 丨嗓]_ 2'(1Ή)-ketone A 4.38 1'-(tetrahydro- 2Η-喊 -2- -2--2-ylmethyl)-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene_8,3,_沔丨哚]-2,(1Ή)-ketone A 4.39 14(5-Chloro-1-methyl-1Η-imidazol-2-yl)indenyl]-2,3-dihydrospiro[furo[2,3 -g][l,4]benzodioxanthene_8 3,_ρ丨哚丨哚]-2'(1Ή)-ketone A 4.41 1_〇 ratio+pyridine_2_based f group&gt;2, 3-Dihydrospiro [bite ° Nanhe [2,3~g][l,4] benzodioxanthene -8,3'-吲嗓]-2,(1Ή)-ketone A 4.43 1 - [(2S)-E9 hydrogen fur -2-ylindenyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthracene 05丨哚2^)-ketone A 4.44 1 - [(2R)-eshydrofuran-2-ylmethyl]_2,3-dihydrospiro[?,[2,3-g][l,4]benzodioxene _8,3' _^卜朵2'(1Ή)-ketone A 4.45 1 -(1,4-Dioxindolin-2-ylmethyl)_2,3_dihydrospiro[吱,[2,3-g][ l,4]benzodioxanthene _8,3'_Ρ5| 〃 ))_ 2,(1Ή)-ketone A 4.46 1 -(3,4-methyl, oxybenzyl)_2,3- Dihydrospiro[ρofran[2,3_g][1,4]benzodioxene _8,3'·(9)哚]_2, (i,h)-ketone A 143924-sp-20091127- 6 994 (s 201020257

Example No. Compound name IC5〇4.47 Γ-(3,5-Dimethoxybenzyl)-2,3-dihydrospiro[Vf-[2,3_g] [1,4]benzodioxanthene Rare -8,3'-吲嗓]_2'(1Ή)-ketone A 4.48 Γ-(2,3-dihydro-1,4-benzodioxanthene-6-yl fluorenyl)-2, 3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthracene -8,3'-啕哚]ketone A 4.49 (11)-1'-{[5 -(trifluoromethyl)-n-butyl-2-yl]fluorenyl}_2,3_dihydrospiro[,,[2,3-g][l,4]benzodioxolene -8, 3,_吲哚]-2'(1Ή)-ketone A 4.50 (S)-l'-{[5-(Trifluoromethylfol-2-yl)methyl}_2,3-dihydrospiro [furo[2,31][1,4]benzodioxanthene_8,3,_吲哚]-2'(1Ή)-ketone A 4.51 (S)-l·7-pyridin-2 -ylmethyl)-2,3-dihydrospiro[,,[2,3-g] [1,4]benzodioxanthene-8,3'-thirsty]-2' (1Ή )-ketone A 4.52 Γ-(10)pyridin-2-ylindenyl)-6,7-dihydrospiro[benzo[l,2-b:4,5-b,]difuran-3,3'-啕哚]-2'(1 ugly)-ketone A 4.53 l'-[(2R)-rahydrofuran-2-ylmethyl]-6,7-dihydro-5H-spiro- s-[3,2- g] terpene-3,3.5 budose]-2\1Ή)-ketone B 4.54 Γ-{[5-(trifluoromethyl)pyran-2-yl]methyl}-3,4-di Hydrogen-2Η-spiral [ Pyrano [2,3-h] [l, 5] benzo-ene -9,3-dioxo Park seven nitrogen.丨哚 丨哚]-Τ(1Ή)-ketone B 4.55 Γ7-pyridin-2-ylindenyl)-3,4-dihydro-2Η-snail [攻喃和[2,3七] [1,5] Benzodiazepine heptarene-9,吲哚]-2'(1Ή)-ketone B 4.56 2-mercapto-indole-(3-methylbutyl)spiro[吱,[2,3-f ][l,3]benzopyrazole-7,3'-吲哚]-2'(1Ή)-ketone C 4.57 2-methyl-indole-(tetrahydro-2Η- sher-4-ylmethyl) Snail [Miso-[2,3&lt;|[1,3] benzopyrazole-7, oxime]-2'(1'11)-ketone C 4.58 2-methyl-14(Han)-tetrahydrofuran -2-ylmethyl] snail [bito-and-[2,3-phan [1,3]benzoxazole-7,3'-嘀哚]-2'(1'11)-one C 4.59 1- Methyl-l'-[(2R)-tetrahydrofuran-2-ylmethylHH-spiro[啥,[3,2-g][l,4]benzoindole-8,3'-吲哚] -2,2·(1Ή,3Η)-dione C 143924-sp-20091127-6 •995- 201020257 Example No. Compound name iQ〇4.60 1-fluorenyl-r-[(2R), hydrofuran-2-based曱基] 螺[吱 并[3'2-f][l,3] stupid and skillful β sitting _7,3'_令朵]_2,2'(1Η,ΓΗ)-dione C 4.61 6-曱oxy-5-methyl_r_[(2R), hydrogenfuran-2-ylmethyl]spiro[1-benzofuran_3,3,_ 哚 哚]-2, (1Ή)-class C 4.62 6-decyloxy-5-methyl(pyridine-2-ylindenyl)spirobenzofuran -3-3,3'-吲哚]_2'(1Ή)-ketone C 4.63 6·曱氧手 methyl-1'-(tetrahydro-; 2Η-喊喃-2-ylindenyl) snail [1- Benzofuran_3,3·-吲哚]_2,(1Ή), C 4.64 5-fluoro-6-methoxy-1,-(tetrahydro-2-indole-piperidin-2-ylindenyl) snail [1-benzofuran_3,3'-啕哚]_2'(1Ή), B 4.65 5-Fluoro-6-fluorenyloxy_ι'_(pyridin-2-ylmethyl) snail Benzofuran-3,3'-吲哚]_2'(ΓΗ)_Steel B 4.66 5-Fluoro-6-methoxy_1'_[(2 ft)-tetrahydrofuran_2_yl fluorenyl] snail [1-benzofuran_3,3·-啕哚]-2'(1Ή)-keto B 4.67 1'-mercapto-5-fluoro-6-methoxyspiro[1-benzofuran_3 ,3,-吲哚]-2'(ΓΗ)-keto B 4.68 6-Methoxy-l'-[(2R)-tetrahydrofuran-2-ylmethyl]spiro[ι_benzofuran-3,3 '-吲哚]-2'(1Ή)-keto B 4.70 1·-{[5-(Trifluoromethyl)pyran-2-yl]methyl}_2,3,6,7-tetrahydrospiro [ ρ夫喝和[3,2-g] bite -5,3^5 noisy]-2,(1Ή)-嗣C 4.72 l'-{[(2S)-5-ketotetrahydropyrrole-2 -yl]methyl} snail [biting and [2,3-f][l,3] benzodioxolanes-7,3'-啕哚]-2'(1Ή)-ketone C 4.73 ( 2'-oxyspiro[吱,[2,3-;〇[1,3]benzodioxanthene) ]-Γ(2Ή)-yl)acetonitrile^ A 4.74 7'-(dioxamethyl)-1'-{[5-(trifluoromethyl)-2-indolyl]methyl} And [2,3-f][l,3]benzodioxolene-7,3,,丨哚]-2'(1Ή)-keto B 4.75 Γ-[(5-carbyl-2- Ruthenyl)methyl]-7'-(trifluoromethyl)spiro 7^^~ and [2,3-£][1,3]benzodioxol-7,3'-吲哚]-2Χ1Ή)-ketone--- B J-— · 143924-sp-20091127-6 -996- 201020257

Example No. Compound name IC5〇4.76 isopropyl, 1,3-inhibited-5-yl)methyl]-7'-(trimethylmethyl) snail [吱,[2,3-f][l, 3] benzodioxolone _7 3, _^丨哚]-2'(1Ή)-ketone' B 4.77 1 -[(2-isopropyl-1,3"-salt-5-yl) Methyl] snail [pf-methane [2,3_ phantom [1,3] benzodioxo oxene-7,3'- noisy]_2'(1 ugly)-ketone A 4.78 [1-ring Propyl-3-(2·-oxaspiro[吱,[2,3-f][l,3]benzodioxanthene-7,3'- lingual]-1'(2Ή)- Phenyl]aminocarbamic acid tert-butyl ester A 4.79 Γ-[4-(methylthio)] ketone] sulphate [2,3-f][i,3]benzodioxene^伍园-7,3W丨哚]-2'(1Ή)-ketone--- A 4.80 3-(2'-oxaspiro[2,3-f][l,3]benzoic Oxygen olefin-7,3 "啕哚]-1'(2Ή)-yl)propanenitrile---- A 4.81 1'-[(2-bromo-1,3-pyrene-5-yl) )methyl]spiro[吱,[2,3_f]~[1,3]benzodioxolene-7,3·-吲哚]_2,(1·Η)-嗣—---- - A 4.82 Amino-4-(trifluoromethyl)-1,3-oxazol-5-yl] fluorenyl} snail ~ bromo-[2,3-f][l,3]benzoic Oxygen oxime _7,3,-啕哚]-2ΧΓΗ)-keto_B 4.83 6-fluoro-5-曱Oxy-1'-{[5-(trifluoromethyl)pyran-2-yl]pyranyl}spiro[1-benzofuran-3,3'-吲哚]-2,(1Ή)- Ketone---.c 4.84 4'-Chloro-2'-oxaspiro[吱,[2,3-f][l,3]benzodioxanthene~ene-7,3'-(4)哚]-Γ(2Ή)-yl)acetonitrile----- B 4.85 Γ-[(2-amino-1,3-thiazol-4-yl)indolyl] snail [吱,[2,3-magic [1,3]benzodioxanthene-7,3·-throindole]-2·(1Ή)-ketone-. B 4.86 4'-bromo-indole-[(5-chloro-2) -ρ塞基基) fluorenyl] snail [吱,[2,3-f][l,3]benzodioxolene-7,3'-吲哚]-2|(1Ή)-one S--^. A 4.87 1'-[(5-Chloro-2-nonyl)methyl]-2·-keto-1',2·-dihydrospiro[吱,[2,3 -f][l,3]benzodioxanthene _7,3'_吲哚]-7'-phthalonitrile----. A 4.88 1·-[(2-isopropyl-1, 3-pyrazol-4-yl)indolyl]-2,-keto-indole, 2'-di-hydrospiro[吱,[2,3-f][l,3]benzodioxanthene Alkene-7,3L 啕哚]-7'-carbonitrile-^~ AJ---- 143924-sp-20091127-6 -997- 201020257

Example No. Compound name IC5〇4.89 4'-Gas-anthracene-[(5-carbyl-2-nonyl)methyl] snail [Miso-[2,3·Π[1,3]benzoic Oxyvalene _7,3'_啕哚]-2·(ΓΗ)-ketone A 4.90 41-Chloro 4-{[5-(trifluoromethyl)-2-oxanyl]methyl} snail [吱喃和[2,3韵1,3]benzodioxolene-7,3',哚]-2,(1Ή)-ketone A 4.91 4·-Chloro-indole-[(2- Isopropyl-1,3-oxazosin-4-yl)methyl]spiro[吱,[2,3-f][l,3]benzodioxanthene knives, 3,-吲哚]-2'(1Ή)-ketone A 4.92 446-(didecylamino)pyridinyl]-Γ-{[2-(1-mercaptoethyl)·1,3-喽嗤-4-yl] Methyl} snail [吱, [[2,3-£][1,3] benzo-oxo octagonal _7,3'-ρ5丨嗓]-2'(1'Η)-嗣B 4.93 3 '-[2-(Fluoromethyl)benzyl]-2,3-dihydrospiro [bito-and-[2,3-g] [1,4]benzodioxolene _8, ι' _茚]_2,(3,H)-keto A 4.94 3-[(Γ-keto-2,3-dihydrospiro[furyl]Nan[2,3-g][i,4]benzoic Oxalene-8,3'-吲哚]-1·(2Ή)·yl)mercapto]benzonitrile A 4.95 Γ-(4-fluoro-3-methoxybenzyl)_2,3_ Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3·-吲哚]_ 2,(1Ή)-ketone A 4.96 4-[(2'-keto-2,3-dihydrospiro- 1; carboxy-[2,3-g][l,4]benzodioxan Terpene-8,3'-吲哚]-1'(2Ή)-yl)methyl]benzonitrile A 4.97 1,-(4-isoxazol-5-ylindenyl)-2,3-di Hydrogen snail [cough and [2 3_g] [1,4] benzodioxene _8,3ι_啕哚]_2, (1,H)_class' A 4.98 1 -{[6-(two Fluoromethyl)p is more than _3_yl]methyl}-2,3-dihydrospiro[p-f-[2,3-g][l,4]benzodioxolene-8, 3'_嘀哚卜2'(ΓΗ)-ketone A 4.99 Γ-(4-isoxazol-5-ylbenzyl)-3-methylspiro[吱, and pm [1,2] benzisoindole Azole_5,3'-啕哚]-2'(1Ή)-ketone' B 4.100 14(5-fluoropyridin-2-yl)methyl]-2,3-dihydrospiro[吱喃[2 ,3-g][l,4]benzodioxanthene-8,3Ί嗓]_ 2,(1Ή)-ketone A 143924-sp-20091127-6 -998-

(S 201020257

Example No. Compound name IC5〇4.101 base p is more than 唆-2-yl) fluorenyl]-2,3-dihydrospiro[pfrano[2,3'[1,4] benzodioxanthene- 8,3'-吲哚]-2,(1Ή)-ketone A 4.102 Γ-(ρ ratio D-but-2-ylmethyl)-4'-ρ奎奎林-3-yl-2,3-di Hydrogen snail [bitillino[2,3-g][l,4]benzodioxanthene-8, 吲哚]_ 2,(1Ή)-keto B 4.103 4'-(4-phenoxy Phenyl)-indole-(acridine!ylmethyl)-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene _8,3,_ρ引' 哚]-2'(1Ή)-keto B 4.104 Γ-[(3,5-Difluoropyridin-2-yl)methyl]-2,3-dihydrospiro[sniffin[2,3- g][l,4]benzodioxanthene _8,3'-p?丨嗓]-2,(1Ή)_ ketone A 4.105 2·-keto-oxime-indole-2-yl Methyl)-indole, 2'-dihydrospiro[μbenzopyrano-3,3'-啕哚]-6-carbonitrile C 4.106 3-{[(8S)-2·-keto-2 ,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene-8,3·-吲哚]-Γ(2Ή&gt;基]曱)benzyl Nitrile A 4.107 (8S)-lj-[(5-fluoropyridin-2-yl)methyl]-2,3-dihydrospiro[吱嗔弁[2,3-g][l,4]本弁Dioxane 圜 _8,3'_p5丨嗓]_ 2Χ1Ή)-ketone A 4.108 (85)-Γ-[(3-^ Pyridin-2-yl)indenyl]-2,3-dihydrospiro [bito-and-[2,3-g][l,4] dioxoline dilute ρ ιι 2'(1Ή)-ketone A 4.109 (S)-l-(2-ketobutyl)-3,7-dihydro-2Η-spiro[benzoheptan[5,6-b][l,4]dioxene -8,3,_dihydroindole]-2, class A 4.110 14(4-fluoroacridinyl-2-yl)methyl]·2,3-dihydrospiro[2,3-g][l , 4] benzodioxanthene _8,3,_巧哚2'(1Ή)-ketone A 4.111 1 -(2,3-Hydrogen-1,4-benzodioxanthene_6 _ylmethyl)·2 yl-1,2-dihydrospiro[μbenzofuran_3,3'_吲嗓]carbonitrile B 143924-sp-20091127-6 •999- 201020257

Example No. Compound name ic5〇AA 4.112 Γ-[(3-气基峨唆1基)methyl]- [2,3-g][l,4] stupid and dioxererene_8 3,吲„ τα'Η)-ketone needle 4.113 1 -[2-(difluoromethyl)-yl]_2,3_dihydrospiro[吱,[1,4]benzodioxolene-8,3, _ Anonymous 4.114 (8R)-l'-[2-(difluoroindolyl)-yl]_2,3_二^^^-- [2,3-g][l'4]benzodiox Luyuan _8,3·-τ»5 Budu 1 2'_-ketone" B 4.116 (8S)-1 -[2-(Difluoromethyl)pinyl]_2,3_dihydrospiro[ρ A total of [2'3-g][l,4] stupid and dioxic orthorhombic _8,3Ί嗓1 2'(1Ή)-ketone AA 4.118 Bu (2,1,3-benzopyrene Zyrid-5-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3·_吲哚 fly 2, (1Ή)-ketone 4.19 Γ-(1,3-benzopyrazol-2-ylindenyl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzo ___ 乳陆园稀-8,3^5丨嗓]-2,(13⁄4) ketone broad AA 4.120 Γ-[(1-mercapto-1H-benzopyran-2-yl)methyl]_2, 3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8 3,_ρ丨丨' 哚]-2'(1Ή)-ketone' 4.121 Γ- {[2-(1-methylethyl)-1,3-soul. -4-yl] fluorenyl}·2,3-digasspin [Miso-[2,3-g][l,4]benzodioxene _8 3, 丨哚]-2Χ1Ή )-ketone' A 4.122 Γ-(2,1,3-benzo-p-di. sit-5-ylmethyl)-2,3-dihydrospiro[唉,[2,3-g][l , 4] benzodioxanthene _8,3'-吲哚]-2'(1Ή)-ketone A 4.124 Γ-(pyridyl-2-ylmethyl) snail [biting mers [3, 2 -e][2,l,3]benzoxadiazole-8,3'-吲哚]-2Χ1Ή)-ketone A 4.125 Γ-(acridin-3-ylindenyl) snail [biting and arranging [3] ,2-e][2,l,3]benzoxadiazole-8,3'-吲哚]-2'(1Ή)-ketone C 143924-sp-20091127-6 201020257

Example No. Compound name iQ〇4.126 6-Chloro-indole-indole-But-2-ylmethyl)-2,3-dihydrospiro[吱,[3,2-f][l,4]Benzene Dioxane ore _9 3, _ old 嗓ι_ 2'(ΓΗ)-ketone C 4.127 Γ-0 than bit -2-ylmethyl)-2,3-dihydro snail [唉 并 [3 2 that , 4] benzodioxanthene -9,3·-^丨嗓]_2, (ι,η)-ketone C 4.129 l-[(2R)-rahydrofuran-2-ylmethyl]-5 ,6,,7,8,_tetrahydrospiro-3,3'-indolo[2,3-b]pyran]-2(1H)-one C 4.130 1 -〇比唆- 2-ylmethyl) snail [吱 并 p p _8 3'_p!| 哚]-2\1Ή)-ketone 'C 5 Γ-[(2-oxime, bite-5-yl) A Base]_5,6_dihydrospiro[benzo[l,2-b:5,4-b']dioxin-3,3'-p?bido i_2, (i,hvketone B 5.1 7' -Chloro-indole-((5-(trifluoromethyl)pyran-2-yl)methyl)_5 6_ 二风-2Η- snail [benzopyrene [6,5-7] 吱 _3 3,_Dihydroindole]-2'-keto B 5,2 (3R)-l'-(3-mercaptobutyl)-5,6-dihydrospiro [Benzene like seven:5,4_b, ] difuran-3, 吲哚]-2·(1Ή)-steel C 5.3 (3R)-1 -mercapto-5,6-one wind snail [stupid [l,2-b: 5,4 seven] ] Two bite taste -3,3'-吲哚]-2丨(1,11)-ketone C 5.4 (3R )-l'-indolepyridin-2-ylmethyl)_5,6,dihydrospiro[benzo[i,2-b:5,4-b']di-n--3,3'-^b ]]-2,(1Ή)-ketone C 5.5 (3R)-l^{[5-(trifluoromethyl)mum-2-yl]methyl}-5,6-dihydrospiro[benzo[ l,2-b : 5,4 7']difuran_3,3,-^丨哚1-2,αΉ)-keto C 5.6 (3S)-l'-indolepyridin-2-ylmethyl) -5,6-dihydrospiro[benzo[i,2-b:5,4-b]difuranium]-2,(1,H&gt;_ A 5.7 (3S)-l^{[5- (Trifluoromethyl) acetophenone-2-yl] hydrazin 5,6·dihydrospiro[benzo[l,2-b:5,47']difuran-3,3,-^丨哚]-2,(1Ή)-ketone A 5.8 3-A--Γ-{[5-(trifluoromethyl)pufan-2-yl]indenyl} snail [吱,[2,3-f] ][l,3]benzoxazole_7,3,-啕哚]-2,2,(1Ή,3Η)-dione C 5.13 14(6-chloropyridin-2-yl)methyl]_2 ,3_Dihydrospiro[2,3-g][l,4]benzodioxanthene_8,3·_ρ5丨哚]_ 2'(1Ή)-ketone A 143924-sp -20091127-6 -1001-

Claims (1)

201020257 VII. Patent application scope: Where: η is 1 or 2; One of J and Κ is -CH2-, and the other is; or both J and K are -CH2 -; R1 is hydrogen, methyl, cyclopropyl, carboxymethyl, (3-carboxy-based, ( 3_Methanesulfonylamino) aryl, [(3-methylsulfonylamino) acridine-2-yl]methyl, [(3-aminoacridin-2-yl)methyl, [( Ethoxy)methyl]methyl, 2-cyclopropylethyl, 1,3-pyrazol-5-ylmethyl, 3-methoxypropyl, (6-fluorenylpyridyl)methyl, Pyridin-3-ylmethyl, [3-(cyano)acridin-2-yl]methyl, [3-(difluoromethyl&gt;pyridin-2-yl]methyl, 3-(5- Methyl-1,2,4-oxadiazol-3-yl)ylidene, 4-(5-methyl-1,2,4-oxadiazol-3-yl)hanyl, [5-(three Fluoromethyl)-1,2,4-oxadiazol-3-yl]methyl, [5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]indolyl, [ 4-(Trifluoromethyl)pyridin-2-yl]fluorenyl'(4-methyl-1,2,5-oxadiazol-3-yl)methyl, pyridin-2-ylmethyl , pyrimidin-2-ylindenyl, (1-methyl-1 fluorene-benzotriazol-5-yl)methyl, [2-(tris-butoxycarbonylamino)pyridin-5-yl]methyl , [6-(Dimethylamino)pyridin-3-yl]methyl, [6-(dioxyl)pyridin-2-yl]methyl{6-[(diphenylene) Amino]pyridin-2-yl}indenyl, (5-morpholine~4-ylpyridin-2-yl)indenyl, [5-(dimethylamino)pyridin-2-yl]indolyl , (6-Aminopyridin-2-yl)methyl, (6-keto-1,6-dihydropyridin-3-yl)methyl, (2-hydroxypyrimidine-5-143924-sp-20091127- 6 201020257 yl), (1-methyl-6-keto-i,6-dihydropyridine _3_yl)methyl, (6. amine-based butyl-3-yl) fluorenyl 'H4 Triazolopyridine-6-indenyl, (5-hydroxyindole-2-yl)methyl, (5-indiylpyridine-2-yl)methyl, decylcarbonylmethyl, [6-deoxy- D-galactose melanose], (6-morphine winter pyridine-3-yl)methyl, [3-(methylsulfonyl)acridin-2-yl]methyl, (4S)- 2,2-dimercapto-1,3-dioxoindol-4-yl]methyl'(3-bromopyridin-2-yl)methyl, [(2-indenylamino) ρ ratio bit-5-yl] fluorenyl, (6-cyano ρ than _2-yl) fluorenyl, (6-aminocarbonyl guanidin-2-yl)methyl, diphenylmethyl, 4 -methoxyindenyl, 2-(fluoromethyl)indenyl, 2-ethoxyethyl, 4-fluorophenyl, (2-fluorophenylaminocarbonyl)methyl, 2-(2- Methoxyethoxy Ethyl, 4-isoxazole-5-ylbenzyl, 3-(benzyloxy)propyl, (2S)-2,3-dihydroxypropyl, 4-methoxybutyl, pentyl, iso Pentyl, hexyl, 3-nitrobenzyl, [3-(trifluoromethyl)pyridin-2-yl]methyl, [5-(trifluoromethyl)acridin-2-yl]methyl, [( Third·butoxycarbonylamino group&gt;pyridin-2-yl]methyl, (3-(trifluoromethyl)P-pyridyl-2-yl)fluorenyl, (5-(trifluoromethyl)pyran -2-yl)methyl, tetrahydrofuran-2-ylmethyl, 3-methylbutyl, cyanomethyl, 4-hydroxybenzyl, 3-cyanobenzyl, 4-fluoroyl Oxy-aryl, 4-cyano-yl-[6-(trifluoromethyl]pyrene-3-yl]methyl, [4_(trisylfluoroindolyl)-1,3-&lt;»唾-2-yl] fluorenyl, (3-fluoro-p-biti-2-yl) fluorenyl, (4-diyl ρ-but-2-yl)methyl, (5-fluoro ρ ratio bite-3 -yl) fluorenyl, (5-1-based π-biti-2-yl) fluorenyl, (3-chloro-based ρ-but-2-yl)methyl, (3,5-difluoropurine -2- Base, fluorenyl, (3-pyridin-3-ylisoxazol-5-yl)methyl, (2,2-difluorocyclopropyl)decyl, 2-ylphenyl, 2,1,3 -Benzo-p-dioxan-5-ylmethyl, 2,1,3-benzene , oxadiazol-5-ylindenyl, 1,3-benzovr-voxazol-2-ylmethyl, (ι_indolyl-1Η-benzopyridin-2-yl)methyl, [2- (1-methylethyl)-1,3-»- oxazole_4_yl] 曱143924-sp-20091127-6 201020257 benzyl, tert-butoxycarbonyl, [1-(tri-butoxycarbonyl) Hexahydropyridine-4-yl] fluorenyl, (2-methoxypyrimidin-5-yl)methyl, (6-methoxypyridine-3-yl)indolyl, (1-oxypyridin-2-yl) Methyl, (3-aminopyridin-2-yl)indolyl, hexahydroacridin-4-ylmethyl, [1-(1-mercaptoethyl)hexahydropyridyl] fluorenyl, (1) Methylhexahydropyridin-4-yl)indolyl, phlofolium-2-ylhydrazino, fluorenylethyl)moffolin-2-yl]methyl, (4-mercapto-purine-2_ Base, fluorenyl, (2S)-morpholin-2-ylindenyl, [(2S)-4-mercapto-porphyrin-2-yl]indolyl, [5-(difluoromethyl) -2-yl]fluorenyl, tetrahydro-2H-piperazin-4-ylindenyl, tetrahydro-2H-chloro-2-ylmethyl, (5-yl-1-methyl-1H-imidazole _2_yl) fluorenyl, (6-a gas p-pyridin-2-yl)methyl, (4,6-dimethoxypyrimidin-2-yl)methyl, [(3-methylaminocarbonyl) Pyridin-2-yl]methyl, aminoethyl) Carbyl pyridin-3-yl]methyl, pyridin-2-ylindenyl, oxetan-2-ylmethyl, M-dioxoindolin-2-ylmethyl, 3,4-dimethoxy Benzyl, 3,5-dimethoxyhanyl, 3-hydroxypropyl, 3-o-phenylenediminopropyl, 3-aminobenzyl, (3-aminocarbonyl) narrow group, (4-Aminocarbonyl)indolyl, (3-N,N-diaminocarbonylcarbonyl), 4-(benzylidene) benzo, 4-fluorobenzyl '2,3-difluorobenzyl , 3,5-difluorobenzyl, 2-chloro-4-fluorobenzyl, fluorenyl (2-fluorophenyl)aminocarbonyl]benzyl, 3-(anthraceneoxycarbonyl), 4-(A Oxycarbonyl), 4-(ethoxycarbonyl)benzyl, 3-(dimethylamino-sulfonyl)benzyl, 3-(3-indolyl-1,2,4-oxadiazole-5 -yl)hanyl, 4-(3-amino-1H-pyrazol-5-yl)), 4-(3-indolyl-1,2,4-indenyl-5-yl)hanyl , 3-(fosfos _4_ylsulfonyl) fluorenyl, 2-(difluoroindolyl)-, (3-trifluorodecyloxy) benzyl, (2-fluoro-trifluorofluorene) Alkyl, (2-fluoro-5-trifluoromethyl)hanyl, (2-trimethylhydroxy) narrow, 3-(amino(hydroxyimino)methyl) aryl, 2-amino-2-(hydroxyimino)ethyl, 6-(N,- 143924-sp-20091127-6 201020257 hydroxyformamidine fluorenylamino)pyridin-3-yl)methyl, 2-(2,2,5-trimethyl-U-dioxo Ethyl-2-yl)ethyl, (4-benzylfosfolin-2-yl)methyl, [(2S)-4-indolyl-norfos-2-yl]methyl, 2,3- Dihydro-1,4-benzodioxanthracene methyl, [5-(trifluoromethyl)pyran-2-yl]methyl, 3-(trifluoromethyl)yl, [3 -(Trifluoromethyl)indol-2-yl]methyl, [4-(trifluoromethyl)acridin-3-yl]methyl, (5-fluorenyloxycarbonyl-2-yl)indolyl , 5-carboxyfuran-2-ylindenyl, 5-(dioxylcarbonyl)pyran-2-ylindenyl, [2-(trifluoromethyl&gt;pyridin-3-yl)methyl, Methylcarbonyl, ethoxycarbonyl, tert-butoxycarbonyl or [(3, 511, 5 & 5, such as 8 〇 1 〇 -2, 2, 7, 7-tetramethyltetrahydro - such as ^ 1 Bis[1,3]dioxoindol[4,5-b:4',5'-d]piperidin-5-yl]indolyl; each R2 is independently hydrogen, hydroxy, amine, (Hexylaminocarbonyl)amino, (cyclopentylaminocarbonyl)amino, benzylamino, (cyclohexylaminocarbonyl)amine, methanesulfonylamino, (methyl)carbonylamino , N, N-two Amidinocarbonyl, (ethyl)carbonylamino, (butyl)carbonylamino, (tri-butyl)carbonylamino, (pentylalkylamino, (hexane)carbonylamino, (methoxy fluorenyl) carbonylamino, cyclobutylcarbonylamino, [2-methoxy (ethoxy) carbonyl amide, (methylsulfonyl) amine, (2-three) Fluorinylphenyl)alkylamino, (cyclohexyl)carbonylamino, (cyclopentyl)carbonylamino, (cyclopropyl)carbonylamino, (phenyl)carbonylamino, bromo, cyano , fluoro, decyl, methoxy, hydroxycarbonyl, methylcarbonyl, tetrapyrrolidinylcarbonyl, aminocarbonyl, decylaminocarbonyl, (2-methoxyethyl)aminocarbonyl, (cyclopropyl) Aminocarbonyl, pentylaminocarbonyl, (cyclobutyl)aminocarbonyl, (cyclopentyl)aminocarbonyl, hexylaminocarbonyl, (cyclohexyl)aminocarbonyl, (4-fluorophenyl) Aminocarbonyl, (4-fluorobenzyl)aminocarbonyl, indole, pyridin-2-ylindenyl)aminocarbonyl 143924-sp-20091127-6 201020257 base, 2-(2-methoxyethoxy)ethoxy, [3(trifluoromethyl)pyridin-2-yloxy, thiol, phenoxycarbonyl , 2-ketodecenyl, 2-ketotetrahydropyrrolyl, morpholinyl, 2-ketopyridyl, benzyloxy, [3-(trifluoromethyl)pyridin-2-yl]methoxy Base, pyridine-2-yloxy, pyridin-2-yloxy, 4-(trifluoromethyl)phenoxy, 2-methyl-l,3-u-propazodazole, 2-amino- 1,3-Wow-4-yl, 6-mercaptoamino)hydantosyl, furan-3-yl, mpyrazol-3-yl, 1Η-ρ 啥-4-yl, 1-indenyl ratio Ollen-4-yl, 5-hydroxy-1H-bamboo, salino, quinone-1,2, 'oxadiazol-3-yl, (6-decylpyridin-3-yl)oxy , 1,3-benzodioxolene _5-yloxy, 4-fluorobenzyloxy, 3,5-dimethylisoxazol-4-yl, phenoxy, 3-methoxy Phenoxy, 4-methoxyphenoxy, 3-morpholine-4-ylphenoxy, fluorofluorophenoxy, 4-methoxyphenyl or 4-phenoxyphenyl; or Two adjacent R2 together with the adjacent carbon to which they are attached form a fused p-sally ring, fused pyridyl group Or a fused dioxoenyl ring; φ is a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or precursor thereof drug. 2. The compound of claim 1 wherein j is _〇_ and κ is -CH2_. 3. A compound according to claim 2, which is selected from the group consisting of: 1 - mercapto-2'-keto-N-pentyl-indole, 2,2',3-tetra-argon-[2,3 -g][i,4]benzodioxanthene -8,3'-&lt;p-dot]-4'- slow decylamine; 1 -(one methyl)_4',6··dimethyl Oxy 2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene-8,3'-峋哚]-2'(1Ή)- (8R)-r-[(2R)-l,4-dioxolyl-2-ylmethyl]-2,3-dihydrospiro [furan 143924-sp-20091127-6 -5- 201020257 [ 2,3$][1,4]benzodioxanthene-8,3'-嘀哚]-(1 ugly)-ketone; Γ-[(6-methylpyridin-2-yl)- ]]-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one Γ-(pyridin-3-ylmethyl)-2,3-dihydrospiro[sn-[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-_ ; (R) -3,7-dihydro-2-indole-spiro[benzofuro[5,6-7][1,4]dioxopinene-8,3 '-Dihydroindole]-2'-one; (S) -2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxene-8,3 ·-吲哚]-2'(ΓΗ)-ketone; 〇(8S)-l'-{[3-(trifluoromethyl)ρ than hexane-2-yl]methyl}-2,3-dihydro Snail And [2,3-g][l,4]benzodioxanthene-8,3'-蚓哚]-2'(1'11)-one; (8S)-r-[(5- Pyridyl-2-yl)methyl]-2,3-dihydrospiro[N-[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2\1Ή)-_ ; 1·-[(5-bromo-based phenylpyridin-2-yl)indenyl]-2,3-dihydrospiro [bito-and-[2,3-g][l , 4] benzodioxanthene-8,3W丨哚]-2'(1Ή)-one; Γ-(diphenylfluorenyl)-2,3-dihydrospiro[吱,[2,3 -g][l,4]benzodioxanthene-8,3%5 bdu]-2·(1Ή)-one; © 6'-isopentyl-3,7-dihydro-2Η- Snail [benzofuro[5 6_b][14]dioxenedecene-8,8'-thiazolo[5,4-e]indole-7'(6Ή)-one; 6-((5 -(trifluoromethyl)pyran-2-yl)methyl)-2,3,3,,7,-tetrahydro-2-indole-spiro[[1,4]dioxolynene[2,3 -f]吲哚-8,8'-benzofuro[5,6_b;][1,4]dioxanthene]-7(6H)-one; 2,3-dihydrospiro[吱And [2,3-g][l,4]benzodioxanthene _8,3,_吲哚]-Τ(1Ή)-one; 143924-sp-20091127-6 201020257 Γ-(3- Methyl butyl)-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxolene-8,3'-啕哚]-2'(1Ή)- Ketone; 1'-(tetrahydro-2Η-scream -4--4-ylindenyl)_2,3-dihydrospich-[2,3-g][14]benzodioxanthene-8,3'-noise]-2·(1 'Η)-ketone; 1'-(tetrahydro-2Η-piperidin-2-ylindenyl)_2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxan Terpene-8,3'-吲哚]-2·(1Ή)-one; 1·-[(5-chloro-1-methyl-1Η-imidazol-2-yl)methyl]_2,3_ Dihydrospiro[Miso-[2,3-g][l,4]benzodioxanthene--8,3'-W 嗓]-2,(1Ή)-one; ® Γ_[(5_ Chloromethyl small methyl-1-hydrazide 'imidazol-2-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene _8 , 3'-吲嗓]·2,(1Ή)-ketohydrochloride; Γ-(pyridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3_g][14] Benzodioxanthene-8,3·-啕哚]-2·(1Ή)-one; Γ-0 to bite-2-ylmethyl)-2,3-dihydrospiro[furan[2] 3_g][14]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one hydrochloride; 14(2S)-whydrofuran-2-ylindenyl]- 2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one; ❿ r-[ (2R)-tetrahydrofuran-2-ylmethyl]-2,3-dihydrospiro[吱,[2,3_§][1,4]benzodioxanthene-8,3 -吲哚]-2'(1Ή&gt;ketone; Γ-(1,4-dioxoindolin-2-ylmethyl)-2,3-dihydrospiro[, benzo-benzodioxanthene- 8,3'-吲哚]-2·(1Ή)-ketone; Γ-(3,4-dimethoxybenzyl)-2,3-dihydrospiro (Vf-[2,3_g][ i,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; Γ-(3,5-dimethoxy)-2,3-dihydro Snail [call D Nanhe [2,3_g][i,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; 143924-sp-20091127-6 201020257 Γ -(2,3-dihydro-1,4-benzodioxanthene-6-indenyl) 2,3-dihydrospiro[furo[2,3-g][l,4]benzo Dioxane orthorax _8,3,...哚]_2,(1Ή)-ketone; (R)-r-{[5-(difluoroindolyl) miso-2-yl]indolyl 2 3 dihydrogen Snail [biting and [2,3-g][l,4]benzodioxanthene oxime]_2, (1Ή) ketone; (S) -r-{[5-(difluorodecyl)吱 _2 _ _ _ _2 _2 _2 _2 _2 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬 咬(Ή)ketone; (S)-l'-(pyridin-2-ylmethyl)_2,3_dihydrospib- oxa[2 3 g][14]benzodioxanthene -8,3 '-吲哚]_2, (1,11)-ketone; Γ-[3-(difluoroindolyl)]],3_3_ Hydrogen snail [吱,[2,3414]benzodioxol]-decene-8,3'-吲"]_2, (1Ή&gt;辋; 5-[(2-keto-2,3-di) Hydrogen snail [furo[2,3_g][14]benzodioxolene _8 3, _ Η Η '(2Ή)-yl)methyl] 啥 _2 2_carboxylic acid methyl ester; Pentyl-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene]^'(1Ή)-one; (8R)- R-[(2S)-l,4-Dioxo orthodonylmethyl]·2,3_dihydrospiro[furo[2,3-g][l,4]benzodioxene _8 ,3,_巧嗓]_2,(1 condition)_ketone; (8S)-1 -[(2S)-1,4-oxo-oxaindole-2-ylmethyl]-2,3-dihydrospiro [吱η南和[2,3_g] ® [1,4]benzodioxanthene _8,3'-1^丨&lt;»多]-2'(1)-ketone; (8S) -r-[(2R)-l,4:氡陆园·2_ylmethyl]_2,3_dihydrospiro[吱3[2,3][1,4]benzodioxanthene _8,3'_哟哚]-2·(1Ή)-ketone; Γ-[2-(2-methoxyethoxy)ethyl]_2,3_dihydrospiro[biting and OgHM]benzene Dioxodecene-8J-吲哚]-2'(1Ή)-one; 5-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][ 1,4]benzodioxanthene_8,3,_峋哚]-1'(2Ή)-yl)methyl]pyran-2-carboxylic acid; 143 924-sp-20091127-6 201020257 N,N-Methyl-5-[(2'--yl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzene And dioxin-terpinene-8,3'-啕哚]-l'(2,H)-yl)methyl]-anthracene-2-carboxylate; (8S)-l'-{[3-( Trifluoromethyl)acridine_2_yl]methyl}·2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3 '_吲哚]_2, (ι,Η)_ketone; (8S)-r-[(5-aminopyridinyl-2)-methyl]-2,3-dihydrospiro[吱[2,3-g][l,4]benzodioxanthene-8,3'-noise]-2'(1,11)-one; Γ-(diphenylmethyl)_7·- Gas-based 2,3-dihydrospiro[唉,[2,3-g][l,4]benzodioxolene-8,3'-啕哚]-2,(1Ή)-one ; 4'-Bromo 4'-(diphenylmethyl)-2,3-dihydrospiro[2,3-g][l,4]benzodioxene-8,3 '-吲哚]-2,(1Ή)-ketone; 4·-bromo-indenyl-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzo Dioxetine-8,3'-吲哚]-2'(1Ή)-one; 1'-(diphenylmethyl)-4'-f-group-2,3-dihydrospiro [2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-2,(1Ή)-one; 1'-(4-fluorophenyl)-2, 3-dihydrospiro[吱,[2,3-g][l 4] benzodioxanthene #-8,3'-吲哚]-2'(1 ugly)-ketone; 1'-(diphenylmethyl)-4'-trendolin-3-yl-2 , 3-dihydrospiro [cough and [2,3-g][l,4]benzodioxanene-8J-吲哚]-2\1Ή)-one; Γ-(diphenylmethyl) -4·-(4-phenoxyphenyl)-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodioxene-8,3' -吲哚]-2·(1Ή)-ketone; 5^·bromo-indole-indolepyridin-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3-g] [l,4]benzodioxanthene-8,3'-啕哚]-2\1Ή)-one; 2'-keto-oxime-indolyl-2-ylindenyl)-1, , 2,2,,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-5·-phthalonitrile; 143924-sp-20091127-6 201020257 5·-Bromo-indenyl-(diphenylmethyl)-2,3-dihydrospiro[snolo[2,3-g][l,4]benzodioxole Cyclodecene-8,3'-啕哚]-2'(1Ή)-one; Γ-(diphenylmethyl)-5'-methyl-2,3-dihydrospiro[味喃[2, 3-g][l,4]benzodioxanthene-8,3·-吲哚]-2'(ΓΗ)-one; 1'-methyl-2·-keto-1·,2 , Τ, 3-tetrahydrospiro[, succinyl [2,3-g][l,4]benzodioxanthene-83-吲哚]-4^·carboxylic acid phenyl ester; 乂5'- two Methoxy-14[5-(trifluoromethyl)pyran-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][l,4]benzoic Oxygen decene-8,3,5丨哚]-2'(1Ή)-one; 4',7'-dimethoxy-l'-[2-(2-methoxyethoxy)B ]]-2,3-dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene-8,3·-嘀哚]-2'(1Ή)- ; 6-[2-(2-methoxyethoxy)ethyl]-2,2',3,3·-tetrahydrospiro[1,4-dioxopinene[2,3-fH哚-8,8'-furo[2,3-g][l,4]benzodioxanthene]-7(6Η)-one; 6Η4-methoxybenzyl)-2,3- Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,8'-[1,3&gt;- oxazolo[5,4-eH 哚]-7 , (6Ή)-ketone; 7'-f-based-2,3-dihydrospiro [glycino[2,3-g][l,4]benzodioxanthene-8,34 哚]- Τ(ΓΗ)-ketone; 4'-glycine-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene]-2' ( 1Ή)-ketone; 4-f-based-2'3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene_8,3,-4丨哚] -Τ(ΓΗ)-ketone; 4'-, quinolate-3-yl-2,3-dihydrospiro[吱,[2,3_g][1,4e and dioxanedecene-8,3' -峋哚]-2, (1' H)-keto; 4·-(4-phenoxyphenyl)-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene 143924*sp-20091127 -6 •10- 201020257 ene-8,3,?丨哚]-2丫ΓΗ)-one; 5'-methyl-2,3-dihydrospiro[吱,[2,3-g][l , 4] benzodioxanthene-8,3,-吲哚]-2'(1Ή)-one; 2,3-dihydrospiro[,,[2,3-g][l,4 Benzodioxanthene-8,8'-[1,3]oxazolo[5,4-e]indole-7'(6Ή)-one; 4W-dimethoxy-2, 3-dihydrospiro[1,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one; 3·-[ 2-(fluoro-indenyl)hamido]-2,3-dihydrospiro[V snoring and [2,3-g][l,4]benzodioxime Luyuan -8, Γ-印]-2'(3Ή),' ; 3- [(2'-keto-2,3-dihydrospiro[,2,3_g][1,4]benzodioxanthene_8 ,3,_ 峋哚]-Γ(2Ή)-yl)methyl]benzonitrile; 1·-(4-fluoro-3-methoxybenzyl)-2,3-dihydrospiro[ρ矢喃[2,3-g][l,4]benzodioxanthene-8,3'- 哚 哚]-2'(1Ή)-_ ; 4- [(2-keto-2, 3-dihydrospiro[furo[2,3-g][i,4]benzodioxolene _8,3,_ 啕哚]-1·(2Ή)-yl)methyl]benzamide Nitrile; L(4-isoxazol-5-ylindenyl)_2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxene-8,3'-吲哚]-2·(1Ή)-ketone; Γ-{[6-(difluoromethyl)pyridin-3-yl]fluorenyl}_2,3_dihydrospiro[furo[2,3-ju] [1,4] Benzodioxanthine _8,3'-1»5丨嗓]_2, (;1 ugly)-keto; 1 -[(5-fluoropyridin-2-yl)methyl ]-2,3-dihydrospiro[furo[2 3414]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-_ ; 1 -[(3-fluoropyridine) -2-yl)methyl]-2,3-dihydrospiro[furo[2,3_g][14]benzodioxanthene -8,3'-吲哚]-2·(1Ή)- 1; 1 -(pyridin-2-ylmethyl)-4'-carboline-3-yl-2,3-dihydrospiro[吱,[2,3_g][1,4] 143924-sp-20091127 -6 • 11 - 201020257 benzodioxanthene-8,3·-吲哚]-2'(1Ή)-_ ; 4'-(4-phenoxyphenyl)_ι, seven-bit bite_2 _ylmethyl)_2,3_dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene-8,3'-吲哚]_2, (1 deduction _ Ketone; 1-[(3,5-di-p-p-pyridin-2-yl)methyl]-2,3-dihydrospiro j&gt; Futangyang (10)]benzodioxanthene-8, 3'-啕哚]-2'(1Ή)-one; 3-{[(8S)-2'-keto-2,3-dihydrospiro[吱And [2,3-g][1,4] benzodioxanthene-8,3'-4哚]-1·(2Ή)-yl]methyl}benzonitrile; (88)-1 '-[(5-Aminopyridin-2-yl)methyl]-2,3-dihydrospiro(;吱11南和[2,3_幻[1,4]benzodioxanthene- 8J-W哚]-2·(ί'Η)-ketone; (8S)-1 -[(3-fluoro-based ρ-but-2-yl)indenyl]-2,3-dihydrospiro[吱And [2,3_g][i,4] benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one; (S)-r-(2-ketobutyl) -3,7-dihydro-2Η-spiro[benzopyrano-ob]!^]dioxene terpene-8,3'-dihydroanthracene-2·-one; fluorine-based bite-2 -yl) fluorenyl]-2,3-dihydrospiro [bito-and-[2,3-g][i,4]benzodioxanthene-8,3'-thirsty]-2·( 1Ή)-ketone; Γ-[(3-carbopyridin-2-yl)indolyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodiox Lunene-8,3'-峋哚]-2·(1Ή)-one; 142-(trifluoromethyl)-yl]-2,3-dihydrospiro[吱,[2,3-g ][l,4]benzodioxanthene-8,3'-蚓哚]-2'(1Ή)-one; (8R)-l'-[2-(trimethyl fluorenyl) aryl] -2,3-dihydrospiro[吱]南和[2,3-g][l,4]benzodioxanthene-8,3'-嘀哚]-2·(1Ή)-one; 5'-Methyl-indole-{[3-(trifluoromethyl) Acridine-2-yl]methyl}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3,-吲哚] Ketone; (8S)-142-(trifluoromethyl)benzyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzo 143924-SD-20091127-6 • 12- 201020257 Dioxoenene-8,3'-峋哚]-2Χ1Ή)-ketone; 4·-Moji-Γ-〇-biti-2-ylmethyl)-2,3-dihydrogen η南和[2,3_g][i 4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-嗣; 1 -(2,1,3-本和ρ塞Diterpene-5-ylindenyl)-2,3-monohydrospiro [bito-and-[2,3-g][i 4]benzodioxanthene-8,3'-吲哚]-2 '(1Ή)-ketone; Γ-(1,3- stupid and V-sodium-2-ylindenyl)-2,3-dihydrospiro[吱,[2,3_g][i,4]benzo Dioxetemene]-2'(1Ή)-one; 14(1-methyl-1Η-benzimidazole-2,yl)indolyl]_2,3-dihydrospiro[吱 并 和 benzo Dioxane 圜-8,3'-W 嗓]-2'(1Ή)-one; Γ-{[2-(1-methylethyl)-l,3-oxazol-4-yl]曱}}-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene _8,3,_叼丨哚]_2, (1Ή)-ketone ; 1 - (2, 1,3-sufficiency and singularly succinyl-5-ylindenyl)-2,3-dihydrospiro[味η南和[2 3_g][14]Benzene bismuth territories -8,3'-,5 buds]-2'(1Ή)-ketone; 4-[(2-mercapto-2,3-dihydrospiro[ρ η南南[2,3-g][l,4]benzodioxanthene _8,3,_ Θ丨嗓]-1·(2Ή)-yl)methyl]hexahydrop ratio Small acid-repellent third ester; 9 Tamarix-benzopyrene-5-ylmethyl)-2,3_dihydrogen food wow and pottery [Μ]benzodioxanthene-8,3·-吲哚] -2,(1Ή)-ketone; 1'-{[6-(trifluoromethyl)pyridin-2-yl]methyl}_2,3_dihydrospiro[furo[2,3-g][l , 4] benzodioxanthene _8 3._吲哚]_2·(1Ή),; Γ-{[2-(trifluoromethyl)pyridine_3_yl]methyl}_2,3_ Dihydrospiro[furo[2,3-g][l,4]benzodioxanthene _8,3Lp?1 嗓]_2'(1 贤)_嗣; Γ-{[3-(three Fluorinyl)pyrazine_2_yl]methyl}_2,3_dihydrospiro[furo[2,3-g][l,4]benzodioxene _8,3ι·哬哚]_2,(1Ή)^ ; 1'-{[4-(trifluoromethyl)pyridinyl]methyl b 2,3_dihydrospiro [furan 143924-sp-20091127-6 -13- 201020257 [ 2,3-g][1,4]benzodioxanthene-8,3,W| 哚]-2,(i,h)-one; 1 [(6-ylpyridin-2-yl) Methyl]_2 3_dihydrospiro[furo[2,3_phantom [14]benzodioxole Terpene-8,3'-啕哚]-2,(1Ή)-class; 14(2-methoxy oxime)methyl]_2,3_dihydrospiro[吱嗔3[2 3 g] [i,4]benzodioxanthene-8,3'-吲哚]-2,(1Ή)-one; 1 -[(6-methoxypyridine-3-yl)methyl]_2 3 _ Dihydrospiro [furan oxime, 3 phantom, 4] benzodioxanthene-8,3,-峋哚]-2·(1Ή)-one; (8S)-1 - (咐耕- 2-ylmethyl)_2,3-dihydrospiro[2,3_g][14]benzodioxanthene-8,3'-吲哚]-2,(ΓΗ)-one; (8S)-1 -[(2-decyloxypyrimidin-5-yl)methyl]_2,3_dihydrospiro (&gt;f-benzodioxanthene-8,3·-峋哚]-2,(1Ή)-net; (8S)-1'-(pyrimidin-2-ylindenyl)_2,3_dihydrospiro[吱,[2,3-g][i,4]benzene Dioxetine-8,3'-吲哚]-2,(1Ή)-_ ; 4·-fluoro-anthracene-{[3-(trifluoromethylidene-2-yl)indolyl 2,3-dihydrospiro[吱,[2,3-旦][1,4]benzodioxene _8,3'-1»丨嗓丨嗓]-2, (1) -嗣; 1'-[(2,2-Difluorocyclopropyl)indolyl]_2,3_dihydrospiro[吱,[2,3_g][i,4]benzodioxanthene- 8,3·-啕哚]-2,(1Ή)-ketone; Γ-methyl-2,3-dihydrospiro[唉,[2,3-g][l,4]benzoic圜 · · 8 8 8 8 8 8 8 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 - - - - 2,3-diaza snail [ρ 喃 并 [2,3-g][l,4]benzodioxolene _8,3,_沔丨哚]-2,(1Ή)-one; (Τ-keto-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene-8,3,-钊哚]-Γ(2Ή)- Acetonitrile; 2-[(2'-keto-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3,- 143924 -SP-20091127-6 -14· 201020257 吲哚Η'(2Ή)-yl) fluorenyl] pyridine-3-carboxylate; 1'-(pyrimidin-2-ylindenyl)-2,3-di Argon snail [吱,[2,3-g][l,4]benzodioxanthene-8,3·-啕哚]-2Χ1Ή)-one; 1 -[(4,6-a) Oxypurine-2-yl)methyl]-2,3-dihydrospich-[2,3_g][i,4] benzodioxanthene-8,3·-&lt;哚]-2·(1Ή)-ketone; (S)-l'-pentyl-2,3-dihydrospiro[Miso-[2,3-g][l,4]benzodioxanthene ·8,3,_ 吲哚]-2'(1Ή)-ketone; (R)-l-pentyl-2,3-dihydrospich and [2,3-g][l,4] Benzodioxanthene _8,3l ® 吲哚]-2'(1Ή)-ketone; Γ-hexyl-2,3-dihydrospiro[ρofran[2,3-g][l , 4] benzodioxanthene _8,3,_啕哚]-2'(1Ή)-one; Γ-(2-cyclopropylethyl)-2,3-dihydrospiro[吱And [2,3_g][1,3]benzodioxanthene-8,3Wh]-2'(1Ή)-one; Γ-(2-ethoxyethyl)-2,3-di Hydrogen snail [吱3[g][13]benzodioxanthene-8,3'-蚓哚]-2'(1Ή)-coch; ❹Γ_(4_methoxybutyl)-2 ,3·Dihydrospiro[吱,[2,3-g][l,3] benzodioxanthene-8J-吲哚]-2·(1Ή)-one; Γ-(3-A Oxypropyl)-2,3 digas snail [味D南和[2,3 g][1,3]benzodioxene-8,3'-蚓哚]-2'(1Ή) -ketone; 1,-(3-nitrooctyl-like dihydrospiro[吱,并[2,3 g][l,3]benzodioxan, rare,ha]-2'(1Ή)- Ketone; 1 αα坐-5-yl fluorenyl)-2,3-- 蔚碑r τ soil)' 虱 虱 [furan[2,3_g][1,3]benzodioxanthene- 8,3'-呻哚]-2'(1'Η)-_ ; Γ-{[5-(Tri Imethyl)峨.定_2_基]甲幻-2,3-Dihydrospich and 143924-sp-20091127-6 -15- 201020257 [2,3-g][l,3]benzodioxanthene _8,31_吲哚]_2,(ιή)-_ ; Γ-{[3-(trifluoromethyl)pyridin-2-yl]indolyl 2,3_dihydrospiro[furo[2, 3-g][l,3]benzodioxanthene_8,3,_啕哚]_2, (1 鲷 鲷; 1·-[(3-峨 -3--3-isoxazolyl) )methyl]_2,3_dihydrospiro[furo[2,3-g][l,3]benzodioxene]_2, (ι'Η),; (8R)-l'- {[3-(Trifluoromethyl)indolepyridinyl-2-yl; I methyl 2,3-dihydrospich-[2,3-g][l,3]benzodioxan Terpene _8,3ι·嘀哚]_2, (ι·η)-ketone; Ν,Ν-dimethyl-3-[(2'-keto-2,3-dihydrospiro[吱喃和[ 2,3-g][l,4]benzodioxanthene-8,3'-W哚]-Γ-(2,Η)-yl)methyl]benzenesulfonamide; _ Γ-[ 3-(ifufolin-4-ylsulfonyl)-yl]_2,3-dihydrospiro[pf-pyrano[2,3-g][l,4] benzodioxanthene- 8,3^吲哚]-2'(1Ή)-ketone; 1L[(4-methyldiazol-3-yl)methyl]-2,3-diazaspiro[2,3- g][l,4]benzodioxanthene_8,3'_吲哚]-2,(1Ή)-one; broad (2'3-difluorobenzyl) -2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene-8,3',吲哚]-2^11)-one; 1'-(3,5-Difluoroindolyl)-2,3-dihydrospiro[吱,[2,3_g][14]benzodioxene-8,3,-4丨哚] -2,(1Ή)-ketone; 〇l'-(4-fluoroaryl)-2,3-dihydrospiro[taste and [2,3_g][14]benzodioxanthene-8, 3,-吲哚]-2,(ΓΗ)-ketone; Γ-(2-carbyl-4-carboyl)-2,3-diindole[c- s[2,3-g][l , 4] stupid and dioxanedecene-8,3'-throindole]-oxime (ΓΗ)-ketone; 14(1-mercapto-1Η-benzotriazol-5-yl)methyl]-2 ,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene _8,3,_沔丨哚]-2,(1Ή)-one; Γ- [(3-三气曱oxy) aryl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodi-16- 143924-SP-20091127-6 (S 201020257 Oxygen-ene-ene-8,3'-吲哚]-2'(1Ή)-one; 1-[(2-fluoro-6-difluoroindolyl)-yl]-2,3-di Hydrogen snail [吱σ南和[2,3-g][i,4]benzodioxanthene-8,3'-thirsty]-2'(1Ή)-one; 1 -[(2- Fluoro-5-difluoromethyl)-yl-2,3-dihydrospiro[吱,[2,3-g][i,4]benzodioxanthene-8,3'-啕哚]-2·(1 Ή)-ketone; 1 -[(2-difluoromethoxy)-yl]2,3-dihydrospiro[吱,[2,3_g][i,4]benzodioxanthene-8J -吲哚]-2'(1Ή)-keto; 1 -[2-(2,2,5-dimercapto-1,3-dioxoindole-2-yl)ethyl]_2,3-di Hydrogen snail [ρ夫味和[2,3-g][l,4]benzodioxanthene·8,3'-吲哚]_2, (ι,Η)-ketone; 7·-fluoro group -Γ-(pyridin-2-ylmethyl)-3,7-dihydro-2Η-spiro[benzofuro[5,6-b][l,4]dioxene _8,3, -indoline]_2'-ketone; 7'-fluoro-indole-((3-(Ζ I methyl azeridin-2-yl)indolyl)-3,7-dihydro-2H-spiro [ Benzofuro[5,6-b][l,4]dioxolysene-8,3,-dihydroanthracene-2,-one; 342-(difluoromethyl)-yl]- 2,3-Dihydrospiro[B-pyrano[2,3-g][l,4]benzodioxolene-8, Γ-茚]-2'(3Ή)-one; 14(5- Fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8,3. 5丨哚]-2'(1Ή)-_ ; (85)-1'-[(5-fluoro?-by- -3-yl)methyl]-2,3-dihydrospiro [biting and [2,3] -Name][1,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one; aryloxy)indolyl]-2,3-dihydrospiro[bite喃[2, 3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; (8S)-l'-[4-(benzyloxy)indole 2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8J-吲哚]-2·(1Ή)-one; {5- [(2'-Mercapto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3,- 143924-sp-20091127- 6 -17- 201020257 吲哚]-1·(2Ή)-yl) fluorenyl]P-pyridyl-2-yl}amino decanoic acid tert-butyl ester; 1'-[3-(yloxy)propane ]]-2,3-dihydrospiro[p-f-[2,3-g][l,4]benzodioxanene-8,3'-蚓哚]-2'(1Ή)- Ketone; (2·-keto-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3,-4 哚]-Γ( 2Ή)-yl)ethyl acetate; r-{[(4S)-2,2-dimercapto-1,3-dioxoindol-4-yl]methyl}-2,3-dihydrospiro[吱 并[2,3-g][l,4]benzodioxanthene _8,3'_啕哚]-2'(1Ή)-one; bromo-indenyl-pentyl-2, 3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3'-choline]-2'(1Ή)-one; 3- [( 2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene _8,3,_ 峋哚]-1' (2Ή )-based thiol benzoate ; 4- [(2'-keto-2,3-dihydrospiro [bito-and-[2,3-g][l,4]benzodioxolene _8,3,_ 吲哚] -Γ(2Ή)-yl)mercapto]methyl benzoate; Γ-[(4-benzylmorpholine-2-yl)indenyl]-2,3-dihydrospiro[吱吱[2 ,3-g][l,4]benzodioxanthene-8,34丨哚]-2'(1Ή)-one; (88)-1'-{[(28)-4-yl吗福普林-2-yl]methyl}-2,3-dihydrospiro [biting u Nanhe [2,3-g][l,4] benzodioxanthene-8,3,-峋哚]-2,(1Ή)-one; 4-[(2'-keto-2,3-dihydrospich-[2,3-g][l,4]benzodioxan Benzene _8,3,_ 吲哚]-1'(2Ή)-yl) fluorenyl] benzoic acid ethyl ester; 2-[3-(2'-keto-2,3-dihydrospiro[furan] And [2,3-g][l,4]benzodioxanthene-8,3^-port 5| 口]-1,(2Ή)-yl)propyl]-1H-isoindole · 1,3(2Κ)-dione; 2-[3-(2'-keto-2,3-dihydrospiro[furo[2,3-g][l,4] stupid and dioxane Terpene-8,3,5丨哚]-1·(2Ή)-yl)propylHH-isoindole-1,3(2H)-dione; (85)-1'-[2-(2 -nonyloxyethoxy)ethyl]-2,3-dihydrospiro[吱,[2,3-笆][1,4] 143924-SP-20091127-6 -18- 201020257 Benzodiox Luyuanene-8,3·-蚓哚]- 2\1Ή)--; 6-[2-(2-decyloxyethoxy)ethyl]_2,3-dihydrospiro[furo[2 3_g][14]benzodioxanthene- 8,8'-[1,3]pyrazolo[5,4-e]吲哚]_7ι(6Ή)__ ; 6·-(pyridin-2-ylindenyl)-2,3-dihydrospiro[唉 并 [2,3_g][1,4] benzodioxanthene -8,8'-[1,3]1»塞°[5,4-6]'^卜朵]- 7'(6,11)-keto; 4',6'-dimethoxy-142-(2-methoxyethoxy)ethyl]_2,3_dihydrospiro[吱,[2, 3-g][l,4]benzodioxanthene_8,3,-吲哚]-2'(1,H)-one; 4Άdimethoxy-1·-(tetra)pyridine-2- Methyl)-2,3-dihydrospiro[吱,[2,3-g][l,4] 本弁·一氧陆圜稀_8,3'-p?|p朵]-2 '(1Ή)-啊; (2'-keto-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3._啕哚]-1'(2Ή)-yl)acetic acid; 1'-methyl-2·--yl-1',2,2',3-tetrahydrospiro[sniffin[2,3$][1 , 4] benzodioxanthene-8,3'-吲哚]-4·-carboxylic acid; 3'-[(3-bromopyridin-2-yl)methyl]-2,3-di Hydrogen snail [cough. Nanhe [2,3-g][l,4]benzodioxanthene-8,1·-茚]-2·(3Ή)-one; 3'-{[3-(methylsulfonyl) Pyridin-2-yl]methyl b 2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxanthene -8, Γ-莽]-2' ( 3-Ή)-ketone; 2-[(2'-keto-2,2',3,3'-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxan) (8-8)-l'-{[3-(diImethyl)pyridin-2-yl]methyl }-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3·-&lt;哚]-2'(1Ή)-one; Ν'-Hydroxy-3-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3' -吲哚]-Γ(2Ή)-yl) fluorenyl] benzocarboximine amide; 143-(5-mercapto-1,2,4-oxadiazol-3-yl)benzyl]-2 3-dihydrospiro[furan 143924-sp-20091127-6 •19· 201020257 P,3-g][l,4]benzodioxanthene _8,3,_巧I 嗓;]_2,(i,h)-ketone; Γ-[4-(5-Mercapto-1,2,4-indenyl)-yl]-, 2-dihydrospiro[fur B-and-I; 2,3-g][ l,4] stupid and dioxane 圜 _8,3,_叼1嗓]-2, (1Ή&gt;ketone; 3- [C-based-2,3-dihydrospiro[吱,[2,3 -g][l,4]benzodioxanthene _8,3,_ 吲哚]-1'(2Ή)-yl) fluorenyl]benzoic acid; 4-[(2·-keto-2 ,3-dihydrospiro[,,[2,3-g][l,4]benzodioxanthene _83,_ 吲哚]-Γ(2Ή)-yl)methyl]benzoic acid Ν1-Hydroxy-2-(2'-keto-2,3-dihydrospiro[N,3-[2,3-g][l,4]benzodioxene-8,3'-吲哚]·1'(2Ή)-yl)acetamidamine; [-{[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]methyl}- 2,3-Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3'-圬丨哚]-2,(1Ή)-one; 2 -(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanene_8,3,_蚓哚]-Γ( 2Ή)-yl)acetamidine; 1·-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}-2,3-dihydrospiro[ Wei C2,3-g][l,4]benzodioxanthene-8,3'-叼|哚]-2,(1Ή)-one; Γ-(3-aminobenzyl)-2, 3-dihydrospiro[2,3-g][l,4]benzodioxanthene -8,3'-^Ι ^ ]-2'(1Ή)-ΚΙ ;Ν-{ 3-[(2'-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-啕嗓]- 1 '(2Ή)-yl) fluorenyl]phenyl}-methyl hydrazine; 1·-[(1-oxypyridin-2-yl)methyl]-2,3-dihydrospiro 2,3-g][l,4]benzodioxanthene-8,3'-呻哚]-2'(1Ή)-one; 2-[(2'-keto-2,3- Dihydrospiro[furo[2,3-g][l,4]benzodioxolene-8,3'-吲哚]-1·(2Ή)-yl)indolyl]pyridine-3- Carboxylic acid; 14(3-aminopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzo 143924-SD-20091127-6 •20- 201020257 -Oxygen lanthanum -8,3'-p5丨嗓]-2·(1Ή)-嗣气气酸; Ν-{2-[(2'-_基-2,3- Dihydrospiro[吱,[2,3-g][i,4]benzodioxolene-8,3'-p?bido]-1'(2Ή)-yl)methyl]p比-(____)} Aromatic amine; Γ-(hexahydropyridin-4-ylmethyl)-2,3-dihydrospiro [bito-and-[2,3-g][l,4] Benzodiox Benzene-8,3W丨哚]-2'(1Ή)-hydrazine hydrochloride; methylethyl)hexahydropyridin-4-yl]methyl b 2,3-dihydrospiro[furo[2, 3-g][l,4]benzodioxanthene _8,3'-吲哚]-2,(1Ή)-keto hydrochloride; r-[(l-fluorenylhexahydropyridine-4 -yl)methyl]-2,3-dihydrospiro[吱,[2,3-g][l,4] 苯benzodioxanthene -8,3'-吲嗓]-2' (1Ή)-ketohydrochloride; Γ-(moffolin-2-ylindenyl)-2,3-dihydrospiro[furo[2,3_§][1,4]benzodioxan Alkene-8,3'-吲哚]-2·(1Ή)-one; 1'-{[4-(1-methylethyl)norfosin-2-yl]methyl b 2 3_dihydrogen Snail [Miso-[2,3-g][l,4]benzodioxanthene] ···(ΓΗ)-ketone; 14(4-methylmorpholine-2-yl)- 2,3-dihydrospiro[吱,南和[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2,(1Ή)- Ketone; φ (8S)-r_[(2S)_morpholine-2·ylmethyl]-2,3_dihydrospiro[吱,[2,3-g][l,4]benzoic Oxygen decene-8,3W丨哚]-2'(1Ή)-one; (8S)-l'-{[(2S)-4-indolyl porphyrin-2-yl]fyl}_2, 3_Dihydrospiro[吱,[2,3-g][l,4]benzodioxolene]_2, (ι,η)-ketone; Γ-{[5-( Fluoromethyl)furan-2-yl]methyl}_2,3_dihydrospiro[furo[2,3-lu][1,4]benzodioxanthene _8,3'_叼1嗓]-2,(;1.1^)-ketone; 4-[(2'-keto-2,3-dihydrospiro[2,3_g][1,4]benzodioxanyuan Alkene_8,3,_啕嗓]-Γ(2Ή)-yl)mercapto]phenylhydrazine; 3-[(2,-keto-2,3-dihydrospiro[[, 3_g][1,4]benzodioxanthene_8,3,_143924-sp-20091127-6 •21· 201020257 啕哚]-Γ(2Ή)-yl)methyl]benzamide; Ν,Ν-dimethyl-3-[(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxene-8 ,啕哚]-Γ(2Ή)-yl) fluorenyl]benzamine; Ν-methyl-2-[(2'-copperyl-2,3-dihydrospiro[biting and argon [2,3] -g][l,4]benzodioxanthene-8,3|-啕哚]-1'(2Ή)-yl)methyl]pyridine-3-carboxamide; Ν-(2-amine Benzyl)-2-[(2'-keto-2,3-dihydrospiroindene odor and [2,3-g][l,4]benzodioxanthene-8,3' -啕哚]-1'(2Ή)-yl) fluorenyl-3-carbamoylamine dihydrochloride; Ν-(2-fluorophenyl)-4-[(2'-fluorenyl-2, 3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene]-Γ(2Ή)-yl) Benzomethane; Ν-(2-fluorophenyl)-2-(2·-keto-2,3-dihydrospiro[吱,[2,3-g][l,4]benzene And dioxin-terpene-8,3'-呻哚]-fluorene (2Ή)-yl)acetamide; Γ-methyl-4'-(2-keto-2Η- benzo-7-yl) -2,3-dihydrospiro[ρ, s-[2,3-g][l,4] benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; 1-methyl-4'-(2-_yltetrahydrop-pyrrol-1-yl)-2,3-dihydrospiro[吱,[2,3-g][l,4] benzodiazepine Oxadecene-8,3'-吲哚]-2'(1Ή)-min; Γ-methyl-4'-morpholine-4-yl-2,3-dihydrospiro[biting and argon [ 2,3-g][l,4] stupodioxanthene-8J-啕哚]-2'(1Ή)-_ ; Γ-mercapto_4'-(2-keto-bite-1 (2Η)-yl)-2,3-dihydrospiro [bito-and-[2,3-g][1,4] benzodioxolene-8,3'-吲哚]-2' ( 1Ή)-嗣; 4-amino-indole-methyl-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3. 5 丨哚]-2'(1Ή)-ketone; Ν-(Γ-methyl-2'-keto_1',2,2',3-tetrahydrospib oxime [2,3-g ][l,4]benzodioxanthene-8,3'-acidyl]-4.-yl)cyclobutanecarboxamide; 143924-SP-20091127-6 •22- 201020257 Ν-(Γ -methyl-2· -keto-1,2,2,3-trihydrospiro [bito-[2,3-g][l,4]benzodioxol-8,3,-吲哚]- 41-yl)-2-(trifluoromethyl)benzamide; Ν-(1·-methyl-2'-keto-1,2,2|,3-tetrahydrospiro [2,3-layer][1,4]benzobis*oxodecene-8,3·-吲哚]-4·-yl)methanesulfonamide; Ν-(1·-mercapto-2 '-keto-1,2,2·,3-tetrahydrospiro [bito-and-[2,3-g][l,4]benzodioxene-8,3'-啕哚] -4'-yl)cyclohexanecarboxamide; N-(l,-methyl-2'-keto-1,2,2,3-trihydrospiro[furo[2,3-g ][l,4]benzodioxanthene-8,3'-峋哚]-4.-yl)cyclopentanecarboxamide; ❿methyl-2'-keto-oxime, 2,2 ·, 3-tetrahydrospiro[furo[2,3-g][丨,4]benzodioxanene-8,3'-啕哚]-4.-yl)acetamide; (1·-Methyl-2,-keto-1,2,2,,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene- 8,3'-吲哚]-4'-yl)cyclopropanecarboxamide; Ν-(Γ-methyl-21-keto-1,2,2,3-trihydrospiro[furan[ 2,3-g][l,4]benzodioxanthene-8,3·-吲哚]-4·-yl)benzamide; 2 -methoxy-N-(l,-methyl-2,-keto-l,,2,2,,3-tetrahydrospiro[furo[2,3-g][l,4] φ private And dioxonate _8,3'_吲哚]_4·-yl) acetamidine; Ν-(Γ-methyl-2'-keto-oxime', 2,2',3-tetrahydrogen Snail [唉,[2,3_g][1,4] benzodioxanthene-8,3'-啕哚]-4,-yl)propanamine; N-(l'-fluorenyl) 2'-keto-l', 2,2',3_tetra-argon snail [eat cum-[2,3_ illusion [1,4] benzodioxanthene -8,3'-p5丨嗓]-4'-yl) anthracene; 2,2-monodecyl-indole-(1·-methyl-2,-keto-indole, 2,2,,3 tetrahydrospiro 2,3_g][1,4] benzodioxanthene-8,3,-呻哚]_4,·yl)propanamine; team (1-mercapto-2-ylyl-1', 2 , 2',3-tetrahydrospiro[, succinyl [2,3_ phantom [1,4] benzodioxanthene·8,3,-anthracene]-4,-yl) hexamethyleneamine; 〆, 143924-sp-20091127-6 _ 23 4 Ο / 201020257 Ν_(Γ_Methyl-2', ki-1·, 2,2,,3-tetraaza snail [吱,[2,3-g ][l,4]benzodioxanthene·8,3,-,哚]-4′-yl)heptanylamine; 2-(2-methoxyethoxy)-indole-(1, -methyl-2,-keto-1,2,2,3-trihydrospiro[吱And [2,3-g][l,4]benzodioxanthene_8 3i_w哚]_4'-yl)acetamide; 1_hexyl winter (1, methyl-2,-keto) -Γ,2,2,,3-tetrahydrospiro[吱,[2,3·§][1,4]benzodioxanthene_8,3,-吲哚]-4,-yl Urea; 1-cyclopentyl-3-(indenyl-indenyl-2,-keto-indole, 2,2,,3_tetrahydrospiro [sweet and succinyl] benzodioxanthene -8,3,-钏哚]-4,-yl)urea; 1-cyclohexyl-3-(fluorenyl-fluorenyl-2,-keto-oxime, 2,2,3-trihydrospiro[吱喃[2,3_g][1,4] benzodioxanthene-8,3,-(penta)]-4,-yl) pulse; N-cyclohexyl-1'-methylketone- Bismuth, 2,2',3-tetrahydrospiro[V futto og]!^]benzoxanthene oxide-8,3,-吲哚]-4'-carboxamide; Ν-cyclopentane Base group 2'-keto group_ι',2,2',3-tetrahydrospiro[, benzo-benzodioxanthene-8,3'-呻哚Μ'-carboxamide; Ν -cyclopropylindolyl 2,-keto-indole, 2,2,,3·tetrahydrospiro [bito-and-[2,3liu,4]benzodioxanthene-8,3'- (4) 哚]-4'-carboxyguanamine; 1,-mercapto-4,-(tetrahydropyrrole small carbonyl)-2,3-dihydrospiro[吱,[2,3_g][14]benzene And dioxeremene-8, 3% 5 Budu]-2 (1Ή)-_ ; Ν-(2-methoxyethyl Η'_methyl 2'-keto, 1', 2, 2,, 3_ tetrahydro snail [sniffin [2,3- g][l,4]benzodioxanthene -8,3'-p?丨嗓]_4'-treazone, N-(4-fluoro-aryl H,-mercapto-2,- Keto-I',2,2,,3-tetrahydronose [biting and Ogm,4] benzodioxanthene-8,3'-啕哚]-4'-carboxamide; N- Hexyl-indole-methyl-2'-keto-indole, 2,2',3-tetrahydrospiro[,2,3_g][1,4]benzodioxanene-8,3 '-(5)哚]-4'-carboxyguanamine; 143924-sp-20091127-6 -24- 201020257 Γ-methyl-2 keto-N-(pyridin-2-ylindenyl)-1|,2 , 2',3-tetrahydrospiro[furo[2,3-g][l,4] benzodioxanthene·8,3&lt;_蚓哚]_4'_retinamide; Ν-( 4-fluorophenyl)-indole-methyl-2'-keto-oxime, 2,2',3-tetrahydrospiro[吱,[2,3-g][l,4] benzodioxole Terpene-8,3'-吲哚]-4'-carboxamide; 4-amino-indole-pentyl-2,3-dihydrospirofuran [2,3-g][ 1,4]benzodioxanthene-8,3'-吲哚]-2·(1Ή)-one; 4·-(benzylamino)-Γ-{[3-(trifluoromethyl) Acridine_2_yl]fluorenyl}-2,3-dihydrospiro[Octa[2,3-g][l,4]benzodioxanthene_ 8,3,-吲哚]-2,(1Ή)-one; 4·-amino-1'-{[3-(trifluoromethyl]&gt;pyridyl]indenyl}-2,3-di Hydrogen snail [glyme [2,3-g][l,4] benzodioxanthene _8,3ι_吲哚]_2·(1Ή)-_ ; heart hydroxy-2,3-dihydrogen Snail [吱,[2,3-g][l,4]benzodioxanthene_8,3,_啕哚]-2'(ΓΗ)-one; heart carboxyl-Γ-mercapto- 2,3-dihydrospiro[,,[2,3-g][l,4]benzodioxanthene-8,3^-吲哚]-2'(1Ή)-嗣; 1' _Methyl 4'-7-pyridinyl-2-yloxy)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzo-'-oxo ]-2'(1Ή)-gang 4'-[2-(2-methoxyethoxy)ethoxy]_ι,_methyl 2,3-dihydrospiro[吱,[2,3 -g][l,4]benzodioxanthene oxime]_2, (ΓΗ)-ketone; Γ-mercapto-4'-{[3-(trioxoyl)p-pyridin-2- ]]oxy}-2,3-dihydrospich-[2,3-g][l,4]benzodioxanthene _8,3,_吲哚]_2'(ιή) 1-keto; 1 -methyl-4-[4-(difluoromethyl)phenoxy]_2,3_dihydrospiro[吱,[2,3-g][i,4] benzodioxole圜 圜 _8,3·-吲哚]-2·(1'Η)-ketone; 4·-(benzyloxy)-fluorenyl-indenyl-2,3-dihydrospiro[味喃[2 ,3_g][1, 4] benzodioxanthene-8, 呻哚]-2·(1Ή)-stuffed 1; 143924-sp-20091127-6 -25- 201020257 Γ-methyl-4'-{[3-(three Fluorinyl)pyridine-2-yl]methoxy}_2,3_dihydrospiro[furo[2,3-g][l,4]benzodioxanthene _8,3,- order ]]_2'(1Ή)-ketone; 4-(6·(dimethylamino)pyridin-3-ylindole,-(pyridin-2-ylindenyl)-3,7-dihydro-2Η-spiro[ Benzofuro[5,6-b][l,4]dioxolene-8,3,_dihydroindole]_2, ketone; 4'-(4-methoxyphenyl) 4' · (10) pyridine_2_ylindenyl)_3,7-dihydro-211_spiro[benzofuro[5,6-b][l,4]dioxolysene_8,3'-dihydroindole嗓]_2,-ketone; Γ-methyl-4'-(1Η-峨-sial-3-yl)-2,3-dihydrospiro[, s-[2,3-g][l,4]benzene Dioxodecene-8,3'-吲哚]-2'(1Ή)-one; 4'-indol-3-yl-indole-methyl-2,3-dihydrospiro [2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1!1)-one; Γ-methyl-4H1H-carbazole-4 -yl)-2,3-dihydrospiro[吱,[2,3-g][l,4]benzodioxolene-8,3W丨哚]-2'(1Ή)-嗣; 1'-mercapto ((1-indolyl-1Η-pyrazol-4-yl)-2,3-dihydrospiro[吱,[2,3-g][l,4] Dioxo-salt dilute-8,3'-吲嗓]_2·(1Ή)-one; Γ-methyl-2'-keto-1',2,2|,3-tetrahydrospiro And [2,3$][1,4]benzodioxanthene-8,3'-啕哚]-4·-carbonitrile; fluorenyl-fluorenyl-2'--yl-hydrazine, 2, 2',3-tetrahydrospiro[2,3_g][1,4]benzodioxanthene-8,3'-吲哚]-4'-carboxamide; Γ-fluorenyl -4H5-methyl-1,2,4-oxadiazole_3_yl)_2,3_dihydrospich-[2,3-g][l,4]benzodioxanthene嘀哚]-2·(1Ή)-鲷; 4'-(3,5-dimercaptoisoxazole-4-yl)_ι,_methyl_2,3_dihydrospiro[furan[2, 3-g][l,4]benzodioxanthene_8,3·-呻哚]-2'(1Ή)-one; Ν,Γ-dimethyl-2'-steel base-1· ,2,2·,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodiazepines, -8,3'-吲嗓]-4·-carboxamide ; 143924-sp-20091127-6 -26 - 201020257 N_cyclobutyl·Γ'methyl-2,-keto-oxime, 2,2,,3-tetrahydrospiro[吱,[2,3- g][l,4]benzodioxanthene -8,3'-啕嗓]-4'- valine amine; Ν'Ν'Γ-trimethyl-2,-keto-oxime, 2 ,2·,3-tetrahydrospiro[吱,[2,3-g][l,4]benzodioxanthene] 4'-carboxamide 4'-(3-Methoxyphenoxy)_Γ_曱yl_2,3_dihydrospiro [bito-and-[2,3_g][1,4]benzodioxanthene -8,3 '-θ卜朵]-2'(1Ή)-ketone; 1'-methyl-4-phenoxy-2,3_dihydrospiro[,,[2,3_g][1,4]benzo Dioxetene-8,3'-吲哚]_2, (i,h),; Γ-methyl-4H3-isofyl phenoxy)-2,3_dihydrospiro And [2,3-g][l,4] benzodioxanthene-8,3,-吲哚]-2,(1Ή)-one; 44(6-decyloxypyridine_3_yl Oxy] hydrazino 2,3 dimer snail [furo[2'3-g][l,4] stupid and diterpene terpene _8 3,_啕哚]_2, (1Ή).; 4'_(1'3_benzodioxanthene-5-yloxy)-1,-methyl-2,3-dihydrospiro[furo[2,34][1,4]benzene And dioxerelmene _8,3,_吲哚]_2, (1) ketone; 4-(4-methoxyphenoxypurine, -methyl-2,3_dihydrospiro喃[2 3 g][14]benzodioxanthene-8,3·-吲哚]-2,(1Ή)-one; Γ-methyl-4-(ρ than 唆-2-yl Methoxy)_2,3_dihydrospiro[吱,[2,3-g][l,4]benzodioxanene-8,3'-吲哚]-2,(1Ή)- Ketone; 1-mercapto-4-(4-fluorobenzyloxy)_2,3_dihydrospiro[吱,[2,3 g][1,4]benzoic Luyuan Rare-8,3W Buduo]_2'(1Ή)-ketone; 4-(4-Fluorophenoxy)_;['_Methyl-2,3_Dihydrospiro[Bit and [2] , 3_ phantom [14] benzodioxanthene-8,3'-p? Budu]-2, (1Ή)-_ ; 1 -(4-hydroxyl group)-2,3-dihydrogen Snail [furo[2,3_g][1,4]benzodioxanthene-8,3,-吲哚]-2'(ΓΗ)-one; 143924-sp-20091127-6 -27- 201020257 Γ-(3-propyl)-2,3_dihydrospiro[furo[2,3_g][1,4]benzodioxanthene-8,3'-吲哚]-2' ( 1Ή)-ketone; 2'-mercapto-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene_8,3, Qiao丨哚]-1 '(2Ή)-carboxylate; 2·-yl-2,3-dihydrospiro[furo[2,3_g][1,4]benzodioxanthene]-1' (2 ·Η)-carboxylic acid third · vinegar; r-{[(3aR'5R'5aS'8aS,8bR)-2,2,7,7-ra fluorenyltetrahydro-3aH-bis[1,3] Dioxane is dilute and [4,5-b : 4',5'-d]piperidin-5-yl]methyl}-2,3-dihydrospiro[,,[2,3-g] [l,4] stupid and dioxane terpene _8,3,_"5 buds]_2,(1Ή)·ketone; 0 6-deoxy,6-(2'-keto-2,3- Dihydrospiro[吱,[2,3-g][l,4]benzodioxanthene-8,3·-呻哚Η·(2,Η) -yl)-D-galactose melanose; Γ-cyclopropyl-2,3-dihydrospiro[1,3_g][1,4]benzodioxene _8,3 , _ 吲哚]-2'(1Ή)-ketone; 1 -ethinyl-2,3-dihydrospiro[furo[2,3-g][i,4]benzodioxanthene _ 8,3,_ 啕哚]-2'(ΓΗ)-ketone; Γ-{[4-(trifluoromethyl)pyridine_2-yl]indenyl}_2,3·dihydrospiro[吱吱[ 2,3-g][l,4]benzodioxanthene _8 3,_10 flowers]_2ι(1Ή) ketone; 41-ethyl aryl-indole-methyl-2,3-dihydro snail [biting and [2,3-g][l,4]benzodioxanthene-8,3'-啕哚]-2Χ1Ή)-one; Γ-mercapto-4'-(2-A --1,3-礼嗤-4-yl)-2,3-dihydrospiro[吱,[2,3_g][1,4] benzodioxanthene -8,3'-noise ]-2·(1Ή)-ketone; 4'-(2-Amino-1,3- far &quot;Spin-4-yl)-1,_methyl-2,3-dihydrospiro[cough [2 3_g][1,4] benzodioxanthene-8,3·-吲哚]_2'(1Ή)-one; 4·-(5-hydroxy-1Η-pyrazol-3-yl) -Γ-曱-based 2,3_dihydrospiro[furo[2,3_g][i,4] 143924-sp-20091127-6 -28- 201020257 benzodioxanthene-8,3,-吲哚]-2'(1Ή)-ketone; Γ-[3-(3-methyl-U4-oxadiazole-5-yl)benzyl]_2,3 dihydrospiro[喃[2,3-g][l,4]benzodioxanthene _8, κ 哚]_2, (1Ή) ketone; Γ-[4-(3-amino-1Η-pyrazole _ 5-yl)benzyl]_2,3·dihydrospiro[吱,[2 3 g][1,4] benzodioxene-8,3·-吲哚]_2,(1Ή)_ Ketone hydrochloride; 144-(3-methyloxadiazole_5yl)benzyl]_2,3 dihydrospiro[furo[2,3-g][l,4]benzodioxan _8,3, ♦来]_2,(1Ή)ketone; 2'-keto-1'-7-pyridinyl-2-ylindolyl η,,2,2ι,3_tetrahydrospiro[吱喃[2 , 3_ phantom [14] benzodioxanthene _8,3,-啕哚]-5,-carboxyguanamine; Γ-[(6-morpholine_4_ylpyridine-3-yl) Methyl]_2,3 dihydrospiro [furan [phantom ^ stupid and dioxane hydrazine dilute ^ heart magic cut - ketone; 1 ·-{[6-(dimethylamine cycline _3_ base] Methyl} 2,3_dihydrospiro[c-buto[2,3-g][l,4]benzodioxanthene_8,3,_ten]_2,(1Ή)one; -{[6-(dimethylamino)pyridin-2-yl]methyl} 2,3-dihydrospiro[furo[2,3-g][l,4] stupid and dioxane 2](1Ή) ketone; 1 -({6-[(-benzylidene)amino]p-pyridyl-2-yl}methyl)-2,3_dihydrospiro[biting and argon [ 2'3-g][l,4]benzodioxolene _8 3, _ Multiply]_2,(1Ή) ketone; Γ-[(5-morpholine_4_ylpyridin-2-yl)methyl]_2,3_dihydrospiro[furo[2,3-g][l , 4] stupid and dioxane ore, ·8,3,_,哚]_2,(1Ή) ketone; 1·-{[5-(dimethylamino oxaridinyl-2-yl) fluorenyl}·2 , 3_ dihydrospiro [biting and condensing [2,3 g][l,4] benzodioxene _8,3'_μBuduo]_2, (r ketone; 1 -[(6- Aminopyridin-2-yl)indenyl]·2,3_dihydrospiro[furobenzobenzodioxene-8,3,-吲哚]-TCl'H)-one; 1-[( 6-keto-1,6-dihydropyridine-3-yl)methyl]_2,3 dihydrospiro[吱然和143924-sp-20091127-6 -29- 201020257 [2,3-g][l , 4] benzodioxanthene _8,3'_p5| 嗓]_2, (i,h)-ketone; 14(2-hydroxypyrimidin-5-yl)indenyl]-2,3-dihydrogen Snail [吱,[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; Γ-[(1-methyl) -6-keto-anthracene, 6-dipyridin-3-yl)methyl]_2,3_dihydrospiro[2'3-g][l,4]benzodioxan Alkene-8,3,-anthracene-2,(1Ή)-one; Γ-[(6-aminoacridine-3-yl)indolyl]-2,3-dihydrospiro[ρ [2,3-g][l,4]benzodioxanthene-8,3'-吲嗓]-2'(1Ή)-one; Ν,-trans-yl-Ν-{5-[(2,-keto-2,3-dihydrospiro[c-buto[2,3_g][1,4]benzodioxanene-8, 3'-,?丨哚]-1'(2'11)-yl)methyl]acridine_2_yl}醯iminocarbamamine; 1'-([1,2,4]three saliva And [i,5-a]pyridine_6_ylmethyl)·2 3_dihydrospiro[,[2,3-g][l,4]benzodioxanthene _8,3 ·- order]_2,(γη)-ketone; 1 -[(23)-2,3-dihydroxypropyl]-2,3-dihydrospiro[吱„南和[2,3-g][ 1,4]benzodioxanthene-8,3'-啕哚]-2'(1Ή)-one; 6-[(2-_yl-2,3-dihydrospiro[吱和和[ 2,3-g][i,4]benzodioxanthene_8,3,_吲哚]-Γ(2Ή)-yl)methyladenidine·2·phthalonitrile; or 6-[( 2'-keto-2,3-dihydrospiro[吱,[2,3_g][1,4]benzodioxanthene_8 3,_吲哚]-Γ(2Ή)-yl) Methyl] acridine 2 · carboxy guanamine. 4. The compound of claim 1, wherein j is _Ch2_ and κ is 〇_. 5. The compound of claim 4 which is 丨4(2R)_tetrahydrofuranyl fluorenyl]_4Η_ snail [吱,[3,2-g][l,3] benzodioxanthene _ 6,3, _+ flower]_2, (1Ή) ketone. 6. The compound of claim 1, wherein each of j and κ is _CH2_. 7. The compound of claim 6 which is selected from the group consisting of: Γ-(diphenylfluorenyl)-6,7-dihydro-5H-spiro[吱,[3,2_g]nonene_3,3W丨哚143924-sp-20091127-6 •30- 201020257 2'(1Ή)-ketone; 6,7-monohydro_5Η_ snail [吱,[3,2_g]decene·3,34哚]A-嗣Or 1-[called tetrahydrofuranylmethyl]-6,?-two gas _5η sbromo and [3,2_g] decene-3,3'-θ| 哚]-2·(1Ή)-one . 8·—Formula (π) compound: β where: each R3a is hydrogen or a fluorine group; R3 is hydrogen, methyl, 3-(trifluoromethyl), less than pyridyl]methyl, 2,5-didecyl (1_methylethyl) -1Η-pyrrol-3-yl]methyl, (3-isopropylisoxazole-5-yl)indenyl, (4-bromo-2-pyromenyl)methyl, benzofuran-2- _ ylmethyl, [2_ decyl-5-(trifluoromethyl)-; ι, 3_carbazole _4_yl] methyl, [5_(4-chlorophenyltrifluoromethyl)furan-3 -yl]methyl, [5-carbyl fluorenyl (trifluoromethyl)_m_ _ P than sept-4-yl]methyl, 5-methoxypyridin-3-yl, 4-bromobenzyl , [(2S)-5-ketotetrahydropyrrol-2-yl]fluorenyl, tert-butoxycarbonyl, cyanomethyl, [5-(trifluoromethyl)-2-indolyl] , (5-Chloro-2_, exemplyl) methyl, (3_ carbyl porphin-2-yl)methyl, [3-(2,6-diphenyl)-5-methyl Carbazole_4~yl]methyl, {2-[4-(trifluoromethyl)phenyl]-i,3-oxazol-4-yl}fluorenyl, (5-phenyl-1,3,4 -oxadiazol-2-yl)methyl, [5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl]methyl, [1,3]carbazolo[4, 5-b]pyridin-2-ylindenyl, (2-isopropyl-i,3-pyrazol-5-yl)methyl, (2-isopropyl -1,3-1,3-oxazol-5-yl)methyl, 3-(third-butoxycarbonylamino)&gt;3-(cyclopropyl)propyl, 4-(methylthio)-yl, 2 -Cyano 143924-sp-20091127-6 •31- 201020257 Ethyl, (2-bromo-l,3-p-plug. Sodium-5-yl) fluorenyl, [2-amino-4-(trifluoro) Mercapto)-1,3-, phenazol-5-yl]fluorenyl, (2-amino-1,3-P-conazole-4-yl)indolyl, (5-gas-based V» thiophene- 2-yl)methyl, [2-(1-methylethyl)-1,3-p-sept-4-yl]indolyl, (5-chloro-1,2,4-ρ2 -3-yl)methyl, (5-alkyl-l,2,4-t»zedan-3-yl)methyl, 4-methoxybenzyl, (2S)-1,4-di Oxygen-2-2-methyl, (2-carbyl-1,3-pyrazol-5-yl)methyl, hydrazine (dimethylamino)-1,3-propazol-5-yl] Methyl, (2-norfosine~4_yl-l,3-p-sept-5-yl) fluorenyl, (2-hexahydrop-bite small group·4,3-oxazole-5- Base, fluorenyl, (2-methoxy-1,3-ρ-pyrazole-5-yl)indolyl, 2-[5-(trifluoromethyl)-1,2,4-&lt;» Sial-3-yl]ethyl, [5-(trimethylsulfonyl)_1,2,4′′di- -3--3-indolyl]methyl, (5-cyclopropyl-1,2,4-indole Diazol-3-yl)methyl, [5-( Fluoromethyl)-1,2,4-oxadiazoleyl]methyl, (5-t-butyldiazolocarbyl)methyl, [5-(1-mercaptoethyl)-l, 2,4-oxadiazol-3-yl]fluorenyl, (4-methylhexahydroindol-1-yl)indenyl, (3-indolyl-2-keto-1,3-tetrahydroindole Oxazino-5-yl) fluorenyl, 2-(1-(methylethyl)amino hexyl hexahydrop-p--3-yl)ethyl, (4-cyano oxet-2-yl) Methyl, [5-trifluoroindolyl-4-(indenyl)aminocarbonylfuran-2-yl]methyl, (5-trifluoroindolyl-4-aminocarbonylfuran-2-yl)methyl , [5-Trifluoromethyl_4-(dimethyl)aminocarbonylfuran-2-yl]methyl, [4-(cyclopropyl)aminocarbonyl-1,3-oxazol-2- Methyl, (2,4-dione-1,2,3,4-tetrahydrobutyrate-5'yl)methyl or [4-(methylethyl)aminocarbonyl-1,3 -oxazol-2-yl]methyl; each R4 is independently hydrogen, a gas group, a bromo group, a trifluoromethyl group, a cyano group, a 6-(diguanylamino group) than a acetyl-3-yl group, a tetrahydrofuran group. Or a furan-3-yl group; a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof . 143924-sp-20091127-6 • 32- 201020257 9. The compound of claim 8 which is selected from the group consisting of: 4'-bromo-2'-oxo[s, sulphur[2,3-f][l, 3] benzodioxanthene-7,3,-吲嗓]-1, (2Ή)-sodium citrate, third-butyl ester; Γ-{[2,5-diindenyl hydrazine methyl ethyl )_m_pyrrole;; fluorenyl} snail [ruthenium [2,3-η[1,3]benzodioxene _7,3'-吲哚]-2·(1Ή)- Net; 7'-Mo snail [sniffing P,3-f][l,3]benzodioxolene-731-啕哚]-2,(1Ή)-one; 14(3-iso Propyl isoxazole-5-yl)methyl] snail [bito-and-[2,3-f][l,3] benzodioxolan-7,3,-吲哚]-2, ( 1Ή)-ketone; 14(4-exyl-2-nonyl)methyl]spirob and [2,3-f][l,3]benzodioxol-7,3' -啕哚]-2·(1Ή)-ketone; Γ-(1-benzofuran-2-ylmethyl) snail [Miso-[2,3-f][l,3]benzodiox Terpene-7,3'-吲哚]-2·(1Ή)-嗣; Γ-{[2-amido-5-(trifluoromethyl)-1,3-oxazol-4-yl]anthracene Snail [furo[2,3-f][l,3]benzodioxolene-7,3'_啕哚]-2·(1Ή)-one; 1-{[5-( 4-oxophenyl)-2-(tri-indolyl)ρ analgesic-3-yl]indenyl}spiro-vector Nanhe [2,3-f][l,3]benzodioxolene-7,3'_anthracene]-2'(1Ή)-one; Γ-{[5-carbyl-1- Methyl-3-(trifluoromethyl)-1 Η-pyrazole 4-yl]methyl} snail [furanyl sulphate [2,3 〇[1,3] benzodioxolene-7,3 '-峋哚]-2,(1,11)-_; Γ-(5-decyloxypyridin-3-yl) snail [ruthenium [2,3-f][l,3] stupid and Oxygen sulphate-7,3'- sorghum]-2'(1'11)-ketone; Γ-(4-bromoindolyl) snail (&gt; fut-[2,3-f][l , 3] benzodiazepine _7,3Ί 哚]-2'(1Ή)-one; l'-{[(2S)-5-ketotetrapyrrole_2-yl]methyl} snail [biting and [2,3_f][i,3]benzo 143924-sp-20091127-6 •33- 201020257 dioxolene-7,3·-啕哚]-2,(1Ή)-one; (2'-oxo[furo[2,3-f][l,3]benzodioxol-7,3,-呻哚]-1,(2Ή)-yl)acetonitrile; 7' -(trifluoromethyl)-1,-{[5-(trimethyl)-2-furanyl]methyl}spiro[吱,[2,3-fl[l,3]benzodiox圜 圜-7,3'-啕哚]-2ΐ(1Ή)-_ ; Γ-[(5-alkyl-2-nonyl)indenyl]_7,_(trifluoromethyl)spiro[吱并和阳耶 (3) benzodioxolanes-7,3,-吲哚]-2,(1Ή)-one; Γ-[(2-isopropyl-l,3- Azole-5-yl)indenyl]_7,-(trifluoromethyl)spiro[furo[2,3-f][l,3]benzodioxolene-7,3,·蜊哚; ]_2,(1Ή)-ketone; 14(2-isopropyl-1,3-oxazol-5-yl)methyl] snail [c-c-[2,3&lt;][1,3]benzoic Oxygen olefin-7,3'-吲哚]-2'(1Ή)-嗣; [1-cyclopropyl-3-(2'-oxaspiro[吱-benzo-benzodioxyl]-7 ,3,啕嗓]-1'(2Ή)-yl)propyl]amino decanoic acid tert-butyl ester; Γ-[4-(methylthio) phenyl] snail [吱 benzo benzodioxole圜 圜 _7,3,_ 4 哚]-2'(1Ή)-ketone; 3-(2'-oxaspiro[furo[2,3-fltu]benzodioxolene-7,3 , 丨哚η, (2ή) _ base) propionitrile; Γ-[(2-bromo-1,3-pyrazol-5-yl)methyl] snail [吱 并[2,3_η[13] Benzodioxol-7,3·-啕哚]-2,(1Ή)-net; Γ-{[2-amino-4-(trifluoromethylthiazole! Base] 曱基} snail [biting 〇 〇 [ [1,3] 本 一 氧 -7 -7,3'-ϊ?5丨嗓]_2, (rH)-ketone; 4'-gas base- 2'-oxyspiro[吱,[2,3邳u]benzodioxanthene-7,3,啕哚]-Γ(2Ή)-yl)acetonitrile; *Γ-[(2-amino group) -1,3-pyrazol-4-yl)methyl]spiro[吱,[2,3 f][1,3^and dioxo 143924-sp-20091127-6 -34- 201020257 ,3·-吲哚]-2,(1Ή)-嗣; 4'-bromo-indenyl-[(5-azepin-2-yl)methyl] snail [bito-benzo-dioxy] Terpene-7,3·-吲哚]-2,(1Ή)-one; l'-[(5-Chlorothiophen-2-yl)methyl]-21-oneyl_ι,, 2,_ Dihydrospiro[吱,[2,3-f][l,3]benzodioxanthene_7χ嗓]_7·_carbonitrile; 1 -{[2-(lfylethyl)_ι, 3_thiazole_4_yl]methylbupropenyl_ι',2,_dihydrospiro[bit,[2,3-f][l,3]benzodioxolene-7,3 , _p5丨哚]_7, _ carbonitrile; 143924-sp-2009ll27-6 gas-germanium-[(5-azepin-2-yl)methyl]spiro[吱咕,[2,3_叩,3]benzodioxanthene- 7,3·-啕哚]-2·(1Ή)-one; ΑChloro-[-{[5-(trifluoromethyl)-2-furanyl]methyloxime [吱,[2, 3耶13] benzodioxol-7,3'-吲哚]ΚΓΗ)-one; ΑChloro-indole-[(2-isopropyl-13-P-----pyrazol-4-yl)indole Snail [吱,[2,3-f][l,3] benzo-oxo- 圜 -7-7,3^5丨嗓]-2'(1·Η)-class; 4-[ 6-(monoamine-based butyl-3-yl)-1'-{[2-(1-methylethyl)-i,3-u-s-cyano-4-yl]methyl} snail [furan [2,3-f][l,3]benzodioxolene _7,3'_吲哚]-2'(1Ή)-one; 14(5-alkyl-1,2,4- Ubioxazol-3-yl)methyl]spiro[furo[2,3-f][l,3]benzodioxol-7,3M丨哚]-2·(1Ή)-one; 4'-Gasyl-l'-[(5-Chloro-1,2,4-oxadiazol-3-yl)methyl] sulphide [吱,[2,3-^][1,3] Stupid and dioxolene-7,3'-啕哚]-2·(1 Ή)-one; l'-(4-methoxybenzyl) snail [bito-and-[2,3-f] [l,3]benzodioxanthene-7,3'-啕哚]-2'(1Ή)-one; 14(2S)-1,4-dioxoindolin-2-ylmethyl] Snail [唉,[2,3-f ][l,3]benzodioxanthene-7,3'-吲哚]-2'(rH)-one; •35· 201020257 l'-[(2-chloro-l,3-p Retazo-5-yl)methyl]spib- oxa[2,3-η[ι,3]benzodioxol-7,3'-吲哚]-2'(1Ή)-one ; 1 -{[2-(dimethylamino)-1,3-ρ-sept-5-yl]methyl} snail [吱η南和[2,3_f][i,3]benzodiox Terpene-7,3'-吲哚]-2'(1Ή)-one; Γ-[(2-hofolin-4-yl-1,3-genin-5-yl)methyl] snail吱 并[2,3_如,3]benzodioxanthene-7,3·-峋哚]-2'(1Ή&gt;ketone; Γ-[(2-hexahydropyridin-1-yl- 1,3-,pyrazol-5-yl)methyl]spiro[p-benzobenzodioxol-7,3·-峋哚]-2·(1Ή)-one; Γ-[(2 -曱-oxy-1,3-1,3-oxazole-5-yl)indolyl] sulphate[2,3_f][i,3]benzodioxyloxy-7,3'_啕哚]-2'(1Ή)-ketone; Γ-{2-[5-(trifluoromethyl)_ι, 2,4-oxadiazol-3yl]ethyl}spib-m-[2,3 -f][l,3]benzodioxanthene·7,3,_啕哚]_2,(1Ή)-one; 4'-aero-1'-{[5-(trifluoromethyl) )·ι,2,4-,diazol-3-yl]indenyl}spiro[吱,[2,3-f][l,3]benzodioxene _7,3 _啕哚]_2, (ι, η)-ketone; 4'-gas-purine-[(5-cyclopropyl-ι, 2,4-oxadiazoleyl)methyl; 1 snail [吱And [2,3-f][l,3]benzodioxole _7,3,_fluorenone; 4'-gas group-1|-{1-[5-(difluorofluorenyl) "二冬,号二唑_3_基]曱基丨螺[吱和和[2'3&lt;1[1,3]benzodioxene_7,3,_啕哚]_2, (1Ή),;Γ-{[5-(difluoroindolyl hydrazine, 2, deuterated diazole _3_yl) fluorenyl} snail [biting and yang hunger (3) benzodioxolene-7, 3'-吲哚]-2,(1Ή)-嗣; 1 -[(5-second-butyl-i,2,4-u-diazole_3_yl)indolyl] snail [2,3 fj[13] benzodioxol-7,3'-吲哚]-2·(1Ή)-one; Γ-[(5-cyclopropyl-indole, 2,4-噚) Diazole _3_yl)methyl] snail [吱 并 阳 - 饥 (3) benzodioxol-7,3,-吲哚]_2'(1Ή)-one; 143924-SP-20091127-6 -36- 201020257 4'-Gasyl-1'-{[5_(1_methylethyl)_12,4_oxadiazole_3_yl]methyl} snail [味喃[2,3&lt;[ 1,3]benzodioxanthene _7,3·_吲哚]_2,(1Ή)_^ ; 1'-{[5-(1-methylethyl)oxadiazoleyl]曱Snail [furo[2,3-f][l,3]benzodioxan _7,3,_吲哚]_2,(1Ή)_ketone; 14(4-mercaptohexahydropyrazine small base) fluorenyl] snails smoldering [2,3 rhyme a] benzodioxan Alkene-7,3'-吲哚]-2Χ1Ή)-one hydrochloride; Μ(3-mercapto-2-keto_ι,3_tetrahydrocarbazole_5-yl)indenyl]spiro[furan And [2,3-f][l,3]benzodioxanthene_7,3·_吲哚]_2Ι(1Ή)-one; Γ_{[5-(Trifluoromethyl)-1,2,4′′diazol-3-yl]methyl}spiro[吱,[2,3-f][l,3] benzodiox Oxalene-7,3,-吲哚]-2,(1Ή)-one; Ν-isopropyl-3-[2-(2,-oxaspiro[吱,[2,3-fJ[l] , 3] benzodioxol-7,3·-W嗓]-1'(2Ή)-yl)ethyl]hexahydropyridine-1-carboxyguanamine; 5-[(2·-oxo snail) [furo[2,3-f][l,3]benzodioxanthene-7,3,-吲哚]-indole (2Ή)-yl)methyl porphin-3-indene nitrile; ·-Mercapto-indole, 2'-dihydrospiro [bito-and-[2,3-f][l,3]benzodioxolene-7,3,-吲哚]-7·-曱Nitrile; N-methyl-5-[(2·-oxaspiro[吱,[2,3-f][l,3]benzodioxol-7,3,-吲哚]-1 '(2Ή)-yl)mercapto]-2-(trifluoromethyl)anthran-3-carboxamide; 5-[(2'-oxaspiro[furo[2,3-f][l, 3] benzodioxanthene-7,3'-吲哚]-1'(2Ή)-yl)methyl]-2-(trifluoromethyl)furan_3_carboxamide; hydrazine, hydrazine -dimercapto-5-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxolene-7,3'-吲哚]-Γ(2Ή) )-yl)methyl]-2-(trifluoromethyl)pyran-3-carboxydecylamine; Ν-cyclopropyl-2-[(2·-oxaspiro[吱,[2,3-f] ][l,3]benzoic圜 圜-7,3·-吲哚]-Γ(2Ή&gt; yl) fluorenyl] 4,3-carbazole-4-carboxyguanamine; 143924-sp-20091127-6 -37- 201020257 N-(l -methylethyl)-2-[(2'-oxaspiro[吱,[2,3-f][l,3]benzodioxanthene-7,3'-啕哚]-Γ (2Ή)-yl)methyl]-1,3-oxazol-4-carboxyguanamine; 14(5-aero-2-pyrryl)indenyl]-4'-[6-(diindole) Aminopyridin-3-yl] snail [snolo[2,3-fl[l,3]benzodioxol-7,3·-,?丨哚]-2·(1Ή)- Ketone; gas-based 2-pyrimenyl)methyl]-4'-(3-heptyl) snail [pyrano[2,3-f][l,3]benzodioxanthene- 7,3'-啕哚]-2'(1Ή)-one; 446-(dimethylaminoidin-3-yl)spiro[吱,[2,3-f][l,3]benzo Dioxolene-7,3'-吲哚]-2'(1Ή)-one; 2.2-difluoro-1'-{[5-(trifluoromethyl)pyran-2-yl]methyl }Snail [V-vector][2,3-f][i,3] benzodioxene-7,3'-吲哚]-2·(1Ή)-one; 2.2-difluoro-Γ -{[5-(Trifluoromethyl)pyran-2-yl]indenyl} snail [吱,[2,3-f][l,3] benzodioxolan-7,3' -吲哚]-2'(1Ή)-ketone; 2.2-difluoro-indole-{[3-(trifluoromethylidene-2-yl]indenyl} snail [吱和[2,34 [13] benzodioxol-7,3'-吲哚]-2'(indol)-one; l'-[(3-carbylthiophen-2-yl)methyl]spiro[furan [2,3-f][l,3]benzodioxanthene-7,3'-吲哚]-2'(1Ή)-one; Γ-{[3-(2,6-two gas Phenyl)_5-methylisoxazol-4-yl]methyl}spiro[furo[2,3-f][l,3] benzodioxanthene_7,3·-峋哚] - Τ(1Ή)-ketone; Γ-({2-[4-(trifluoromethyl)phenyl]n, pyrazole-4-yl}methyl) snail [吱-[2,3-f] [l,3]benzodioxolene-7,3'-钊哚]-2'(1Ή)-one; Γ-[(5-phenyl-1,3,4-oxadiazole-2 -yl)methyl]spiro[N-[2,3-f][l,3]benzodioxol-7,3'-啕哚]-2,(1Ή)-鲷; lW[ 5-(4-Phenylphenyl)-1,3,4-oxadiazol-2-yl]methyl}spiro[啥3[13 3 benzodioxol-7,3'-峋哚]-2'(1Ή)-ketone; 143924-sp-20091127-6 • 38- 201020257 Γ-([1,3] rugged[4,5-b]pyridin-2-ylmethyl) snail [furo[2,3-ί][1,3]benzodioxanthene-7,3,-吲哚]-2·(1Ή)-one; (7S)-4'·biting base -1'-methylspiro[吱,[2,3-f][l,3]benzodioxol-7,3'-rhodium]-2'(1·Η)-one; (7 R)-4'-吱然·3·基_Γ_曱基螺[吱,[2,3_叩,3]benzodioxanthene-7,3'-吲哚]-2· (1Ή)-ketone; (7RMW odor-l-L-methyl snail [吱邱和[之邱(10)] benzodioxolane _7,3,-吲哚]-2Χ1Ή)-one; A (7SK- Bromo-indenyl-methylspiro[吱,[2,34^]benzodioxolene-7,3,_ 哚 哚]-2'(1Ή)-one; (7S)-4·-吱 -3--3-yl snail [biting fused [2,3-f][l,3] benzodioxobicin _7,3,_p?j 哚]-Τ(1Ή)-ketone; (7R -4_-furan-3-ylspiro[吱,[2,3-f][l,3]benzodioxolene-7,3ι_4丨哚]-2'(1Ή)-one; 1 '-Methyl-4'-(tetrahydrofuran-3-yl) succinphin and cations of benzodioxole φ ene-7,3'- 哚 哚]-2'(1Ή)-_ ; or 6-[(2^ oxo[吱,[2,3-f][l,3]benzodioxolene-7,3,_,哚] r(2,H)_yl) A Pyrimidine-2,4(1H,3H)-dione. 10. - Formula (ΙΠ) compound: Wherein: m is 1 or 2; 143924-sp-20091127-6 39-201020257 One of L and Μ is _Ch2-, and the other is; R5 is hydrogen, sulfhydryl, hydrazine-4-ylmethyl, two Benzoyl, 4-decyloxybenzyl, 4-benzyl, (5-(trifluoromethyl)pyranyl-2-yl) fluorenyl, tetrahydro-2H-pyran-2-ylindolyl , tetrahydro-2-indole-piperazin-4-ylindenyl, tetrahydro-2-indole-piperidin-3-ylindenyl, (2-carbyl fluorenyl-1 Η-imidazol-5-yl) fluorenyl, 2R)-tetrahydrofuran-2-ylmethyl, (2S)-tetrahydrofuran-2-ylindenyl, tetrahydrofuran-3-ylmethyl, tetrahydrofuran-2-ylindenyl, 3-mercaptobutyl, pentyl 5- (methoxycarbonyl)pyran-2-yl, 1,4-dioxoindole-2-ylmethyl, [1-indolyl-3-(trifluoromethyl)-indole-pyridin-4-yl Methyl, 4-oxime oxycarbonyl-l,3-, oxazol-2-yl, 2-fluorobenzyl, 4-parafluorobenzyl, benzyl '4-phenylbenzyl, (3-bromo) Isoxazol-5-yl)methyl, (5-bromofuran-2-yl)methyl, propylene oxide-2-ylmethyl, (1-ethyl-1Η-imidon-5-yl) Indenyl, 3-cyanobenzyl, 4-cyanoindolyl 4-(2-cyanophenyl)hanyl, 2-[(yloxy)decyloxy]propyl, 2,3-di Hydrogen-1,4- And dioxin-terpinene-6-ylmethyl, 2,1,3-benzoxazol-5-ylmethyl, 2,1,3-benzoxazol-5-ylindenyl, 4-benzylfosfolin-2-yl)decyl, [1-(tris-butoxycarbonyl)tetrahydropyrrol-3-yl]methyl, [(2S)-l-(third-butoxy Carbonyl)tetrahydropyrrol-2-yl]methyl, [1_(tris-butoxycarbonyl)hexahydropyridyl)-yl, [5-(trifluoromethyl)pyran-2-yl]pyrene , pyridin-2-ylindenyl, 4-(methylthio)-yl, (2-methoxypyrimidin-5-yl)indolyl, (2R)-1,4-dioxane-2- Methyl, 2-(2-methoxyethoxy)ethyl, [(2S)-5-ketotetrahydropyr-2-yl]methyl, 2-(2-keto-1,3 - tetrahydropyridin-3-yl)ethyl, 4-p butyl-2-ylbenzyl, pyrimidin-2-ylmethyl 'pyrimidine _4_ylmethyl, ρ than cultivating-2-yl hydrazine , (7-fluoro-1-benzo-dopyridyl-2-yl)methyl, β-indole-3-ylmethyl, (2-keto-1,3-tetrahydrocarbazol-5-yl )methyl, 3-(;oxy)-yl, (1-indolyl-1Η-benzopyrim 143924-sp-20091127-6 . 40 (S 201020257 oxazol-2-yl)methyl, 2H-benzo Triazol-2-ylindenyl, 2-oximeoxycarbonylbenzyl, 4-anthraceneoxycarbonyl , 3-(benzyloxy)propyl, hexahydropyridin-4-ylindenyl, [1-(1-methylethyl)hexahydroindole-4-yl]methyl, (1-ethyl Hexahydropurine-4-yl) fluorenyl, (1-indolylhexahydropyridin-4-yl)indolyl, (2S)-tetrahydropyrrole-2-ylindenyl, 3-retinyl, 2 - Rebellion of the base, 4-sodium base, 4-(yloxy), 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl] , 4-(5-fluorenyl-1,2,4-oxadiazol-3-yl)benzyl, (5-pyridin-4-ylfuran-2-yl)indolyl, 4-pyridine-3- Base group, (2'-fluorobiphenyl-4-yl)indolyl, 3-(5-methyl-1,2,4-shenoxadiazol-3-yl)-yl, 3-[5 -(Trifluoromethyl)-1,2,4-oxadiazol-3-yl]-, 4-(5-fluorenyl-4H-1,2,4-triazol-3-yl)benzyl , 3-hydroxypropyl, morpholin-2-ylmethyl, (4-mercapto-oxafolin-2-yl)methyl, [4-(1-methylethyl)morpholine-2- Methyl, 4-(1Η-tetrazol-5-yl)benzyl, 3-hydroxybenzyl, 4-morpholin-4-ylbenzyl, tetrahydropyrrol-3-ylmethyl, [1 -((1-decylethyl)aminocarbonyl)tetrahydropyrrol-3-yl]methyl, [(2S)-1-methyl-5-ketotetrahydropyrrol-2-yl]indolyl, 3- (ring Amino)carbonylbenzyl-3-[(2-decyloxy)amino]carbonylbenzyl, 3-[(hexyl)(fluorenyl)amino]carbonylcarbonyl, 3-[(2-ethyl) Butyl)amino]hexyl, 3-[(2,4-dimethylphenyl)amino]carbonylbenzyl, 3-[(2-phenylpropyl)amino]carbonylbenzyl, 3-[((lS)-l-cyclohexylethyl)amino]benzylidenebenzyl, 3-[((lR)-l-cyclohexylethyl)amino]carbonylbenzyl, 2-[(4 -ethylphenyl)amino]carbonylbenzyl, 2-[(2-ethylphenyl)amino]carbonylbenzyl, 2-[(2,4-dimethylphenyl)amino] cyclyl Mercapto, 2-[(2-indolylphenyl)amino]carbonylbenzyl, 2-[(2-fluorophenyl)amino]carbonylindenyl, 2-[(3-chlorophenyl)amino Carbonylbenzyl, 2-[(3-fluoro-2-indenylphenyl)amino]carbonylbenzyl, 2-[(heptyl)amino]carbonylbenzyl, 2-[(2-chlorobenzyl) Amino]carbonylbenzyl 143924-sp-20091127-6 -41 - 201020257 base, 2-(hexahydropyridin-1-yl)carbonylbenzyl, 2-[(butyl)amino]carbonylbenzyl, 2 -[(3-methylphenyl)amino]methylidene, 2-[(2-fluoro-5-nonylphenyl)amino]carbonylcarbonyl, 2-[(2,3-di) Methylphenyl)amino]carbonylcarbonyl group 2-[(2-(4-indolylphenyl)ethyl)amino] thiopurinyl, 2-[(3-chlorophenyl)amino]carbonylbenzyl, 2-[(2-(4) -oxyphenyl)ethyl)amino]carbonylcarbonyl, 4-[(2-indolylphenyl)amino]carbonylbenzyl, 4-[(2-trifluorodecylphenyl)amino]carbonyl Benzyl, 4-[(phenyl)amino]carbonylbenzyl, 4-[(methyl)amino]carbonylindenyl, 4-[(2-fluorophenyl)amino]carbonylbenzyl, 4- [(2-Ulexen-2-ylethyl)amino]carbonylbenzyl, 4-(amino)carbonylbenzyl, 4-[(2,3-dihydro-1Η-indol-5-yl)amine ® carbonyl benzyl, 4-(morpholin-1-yl)carbonylbenzyl, 4-[(2-ethylphenyl)amino]carbonylbenzyl, 4-[(2,6-dioxin) Phenylphenyl)amino]carbonylbenzyl, 4-[(3-fluorophenyl)amino]carbonylbenzyl, 4-[(2,4-didecylphenyl)amino]carbonylbenzyl, 4 -[(Umimiphen-2-ylmethyl)amino]benzylidenebenzyl, 4-[(ethyl)amino]carbonylbenzyl, 4-[(2-methoxyethyl)amino] Benzyl, 4-[(2-ethoxyethyl)amino]carbonylbenzyl, 4-[(cyclobutyl)amino]carbonylbenzyl, 4-[(1,3-pyrazole-2) -amino)amino]benzamide, 4-[(3-fluoro-2-indenylphenyl)amino] Oxylcarbonylbenzyl, 4-[(2-ethylbutyl)amino]carbonylbenzyl, (aminocarbonyl)indenyl, [((4-ethylphenyl)amino)carbidyl]methyl, [((2,5-dimercaptophenyl)amino)carbonyl]methyl, [(diethylamino)carbonyl]indenyl, [(3,3-dimercaptobutylamino)carbonyl] A , [(3-(1-methylethoxy)propylamino)carbonyl]methyl, [(propylamino) ketone]methyl, [(phenyl)(fluorenyl)aminocarbonyl] fluorenyl, [((2,4-Dimethylphenyl)amino)]yl]methyl, [((2,3-dimethylphenyl)amino)]methyl], [((2,6) - dimethylphenyl)amino) thiol]hydrazino, (5-carboxyfuran-2-yl)methyl, [5-(dioxylcarbonyl)furan-2-yl]methyl, 143924- Sp-20091127-6 42 (S 201020257 [5-(decylcarbonyl)furan-2-yl]methyl, [4-(aminocarbonyl)-l,3-oxazol-2-yl]methyl, [4-((Dimethylamino)))-1,3-oxazol-2-yl]methyl, 2-hydroxypropyl, (2S)-2-hydroxypropyl, 2-(oxy) , propyl, 2-(4-fluorobenzyloxy)propyl, 2-indolyl-2-yloxy)propyl, 3-hydroxybutyl, 4,4,4-trifluoro-3- Hydroxybutyl, 3-amino Propyl, 3-ketopropyl, 3-[(3-mercaptobutyl)amino]propyl, 3-[butyl(methyl)amino]propyl, 3-[(2,2, 2-trifluoroethyl)amino]propyl, 3-[(2-trifluoromethoxyphenyl)alkylamino]propyl or 3-[(2-cyanoethyl)amino]propyl And _ each R6 is independently hydrogen, gas, bromo, fluoro, methyl, cyano, amine, -C(0)H, -CH2-N(CH3)2, (tetrapyrrole-1 -yl)methyl, 6-(dimethylamino)&gt;pyridin-3-yl, 2-(4-fluorophenyl)ethenyl, dibenzoanthenyl-4-yl, benzothiophene- 3-yl, 1-indenyl-1H-indol-5-yl, 3,5-di(trifluoromethyl)phenyl, 4-phenoxyphenyl, 4-(2-methylpropoxy) a phenyl group, a 4-butoxyphenyl group, a 4-decyloxyphenyl group, a sneezing _5-yl group or a p-propan-3-yl group; or two R6 groups together with the adjacent carbon to which they are attached a fused dioxin φ ruthenyl ring or a fused pyridyl ring; a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, Solvate or prodrug. 11. The compound of claim 1 wherein L is _〇_ and M is _CH2 _. 12. A compound of the claim lamp, which is selected from the group consisting of: (3R)_5,6, dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3W丨哚] -2'(1Ή)-ketone; (10)_5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-吋丨哚]-2, (1Ή )-ketone; 1-oxime-4-ylindolyl)·5 6_dihydrospiro[benzo[12:5:7,]difuran·3 3,_, 哚]々'(ΓΗ) -鲷; 143924-sp-20091127-6 •43- 201020257 4-Alkyl-1'-(diphenylmethyl)_5,6·digas snail [stupid and like seven: 5 state difuran _3,3, _ p 哚 哚 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 -2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 _ 吲哚]-2'(1Ή)-ketone; 1-(monophenylmethyl)-6'-fluoro-5,6-dihydrospiro [stupid (10) seven: 5 4 7] difuran _3, 3, _ 啕哚]-2'(1Ή)-ketone; 7-chloro-1'-(diphenylmethyl)_5,6-dihydrospiro [stupid [^2 seven: 5, 4 seven,] Difuran_3 3,_ ρ 丨哚 丨哚]-2'(1Ή)-one; ❿ 1 -(monophenyl)-4·-fluoro-7'-mercapto-5,6-dihydrospiro [Benzo-, 2-7: 5,4-b']difuran-3,3^吲哚]-2'(1Ή)-one; 1-(monophenylmethyl)-7'-fluoro-5 , 6-dihydrospiro [benzoan like seven: 5,4-7]difuran_3,3,_啕哚]-2'(1Ή)-one; 6-((5-(difluoromethyl)furan-2-yl)indolyl)_2,3, 5,6,-Tetrahydro-2Ή-spiro[[1,4]dioxolysine[2,3-f]吲哚-8,3'-benzofuran[6,5_b] ]_7(6Η)__ ; 6-(((R)whydrofuran-2-yl)methylbu^仏tetrahydro^ snail 叽^ Dioxane 圜 并 [2,3-fH 卜 -8 , 3'-benzopyrene. Nanhe [6,5-b] sniffing n South]_7(6H)-iiq ; 4-alkyl-5,6-monohydrospiro[benzo[i,2-b : 5,4-b,]difuran _3,3,_ 哚 哚]_2, (i'h)_ ketone; 5 - I group-5,6- —hydrosiro[benzo[l,2- b : 5,4-b'] two biting bee _3,3'_p5 丨 mouth]-2'(1Ή)_ ketone; 6-fluoro group-5,6--hydrospiro[benzo[i,2- b : 5,4-b·]二ρ失喃_3,3,_u5卜朵]-2'(1'Η)_ ketone; 7-nitro-5,6-dihydrospiro[benzo[i] ,2-b : 5,4-b]二ρ夫卜布多]-2,(1Ή)_ ketone; 143924-sp-20091127-6 -44- 201020257 7 -Fluoro-5,6-one snail [Benzo[l,2-b:5,4-b'] two bite _3,3Ί 嗓]_2,(γη)· ketone; 4-carbyl-7-mercapto-5,6-dihydro Snail [stupid [1,2 7:5,4-b'] dioxin _3,3,_吲哚]-2'(1Ή)-ketone; 1'-(tetrahydro-2Η-mark drink- 2-ylindenyl)-5,6-dihydrospiro[stupid and like seven:5,4-7,]difuran-3,3'-indole]-2'(1Ή)-one; 1·-[ (2-Chloro-small methyl-1Η-imidazol-5-yl)methyl]_5,6-dihydrospiro[benzo:5,4-b]difuran-3,3'-θ丨哚]- 2·(1Ή)-ketone; ® 14(2R)_tetrahydrofuran-2-ylmethyl]_5,6-dihydrospiro[{,2-b:5,4-7']difuran-3, 3'-啕哚]-2'(1'11)-ketone; Γ-(3-methylbutyl)-5,6-dihydrospiro [stupid [l 2_b : 5,4 b.] THF Taste _3,3,吲哚]-2'(1Ή)-ketone; 1'-[called tetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[[:5, 4 seven kernels scented -3,3,?丨哚]-2Χ1Ή)-ketone; 1'-(tetrachloro-2H- brityl ice-methyl)&gt;5,6-dihydrospiro[benzo-like seven: 5,4,7,]di-pyran-3,3'-啕哚]-2'(1Ή)-one; 5-[(2'-keto-5,6-dihydrospiro[benzo[coffee: 54 VII,]difuran _33, ^丨嗓]-1'(2Ή)-yl) fluorenyl] 吱 叛 叛 甲 . .. 1,-(1,4-dioxoindole-2-ylindole Base)_5,6_dihydrospiro[stupid and like seven··5,4-7]disin-3,3'-吲哚]-2'(1Ή)-one; 1,-{[1-曱Benzyl-3-(tri-1methylhydrazine-hydrazine) sits 4_yl]methyl}56 diazane snail [stupid [l,2-b: 5,4-b·] Difuran-3,3,-吲哚]_2, (1,Η),; 1,-(tetrachloro-2Η-jung-3-ylindenyl)_5,6-dihydrospiro[benzo[ :5,4 别二喃-3,3'-啕哚]-2'(1Ή)-ketone; Free 143924-sp-20091127-6 •45- 201020257 2-[(2'-keto-5,6 - dihydrospiro[benzo[[7:5,4-b,]difuran-3,3,-啕嗓]-Γ(2Ή)-yl)indolyl]-1,3-p saliva_4 _ tartrate; Γ-(2-fluorobenzyl)-5,6-dihydrospiro[benzopyrene: 5,4_b,]difuran_3,3,_,5丨哚]-2' (1Ή)-嗣; 1·-(4-Alkyl)-5,6-dihydrospiro[Benzo-like: 7:5,4-b,]difuran-3,3,-啕哚]-2 '(ΓΗ)-ketone; Γ-爷基-5,6-dihydrospiro[benzo[1,2:7:5,4-b,]difuran-3,3,-'I5丨哚]-2 ,αΉ)-ketone; Γ-(biphenyl-4-ylindenyl)-5,6-dihydrospiro[benzo[nb:5,4_b,]difuran_3,3,_啕哚]-2 '(1Ή&gt;ketone; [_(tetrahydrofuran-3-ylmethyl)-5,6-dihydrospiro[benzo[[7:5,4_b,]difuran-3,3·- 哚 哚]-2 ·(1Ή)-ketone; 14(3-glycosylisoxazole-5-yl)methyl]_5,6-dihydrospiro[benzo[12-7:5 4 b,]difuran-3,3' -吲哚]-2ΧΓΗ)-ketone; 14(5-mentylfuran-2-yl)methyl]_5 , 6_ diars spiro[benzo[12-7:5,4 b,]difuran-3,3'-吲哚]-2'(1Ή),; 1 -(tetrahydrofuran-2-ylindenyl)- 5,6-dihydrospiro[benzo[7:5 4 b,]difuran-3,3'-啕哚]-2'(1Ή)-one; Γ-( propylene oxide-2-yl hydrazine -5,6-dihydrospiro[benzo[12-7:5 4-7,]difuran-3,3'-β 哚]-2·(1Ή)-one; 1 -[(1-ethyl -1Η-Mimi-5-yl)methyl]_5,6-dihydrospiro[benzo[12 b : 54b,]difuran-3,3'-啕哚]-2'(1Ή)-one; 3-[(2,-keto-5,6-dihydrospiro[benzo[12-7: ,,]difuran_3 3, (5) 哚]-1'(2Ή)-yl) fluorenyl] awkward Nitrile; 143924-sp.20091127-6 201020257 4-((2·-keto-5,6-dihydro-2H-spiro[benzofuran[6,5 havufu Nan_3,3, dihydrogen咤哚]-Γ-yl)methyl)benzonitrile; 4-[(2-mercapto-5,6-dihydrospiro[benzo[1,2:7:54,]difuran_33,_11丨哚]-Γ(2Ή)-yl)methyl]biphenyl-2-carbonitrile; 1 -{(2S)-2-[(decyloxy)decyloxy]propyl b 5,6_ Dihydrospiro[benzo[12 b : 5 4_b,] difuran-3,3M budo]-2·(1Ή)-one; Γ-(2,3-dihydro-1,4-benzodioxine Luyuan _6_ylmethyl)5,6 diterpene [benzene And [l,2-b: 5,4-b']difuran-3,3·-吲哚]ΚΙΉ);; 2,1,3-benzooxadiazole-5-ylindenyl) -5,6-dihydrospiro[stup [[7:5,4,7], difuran-3,3W丨哚]-2'(1Ή)-one; Γ-(2,1,3·benzo Thiazol-5-ylmethyl)-5,6-dihydrospiro[benzo-like seven:5,4_bi]difuran-3,3'-吲哚]-2\1Ή)-one; Γ-[ (4-Benzylmorpholine-2-yl)methyl]-5,6-dihydrospiro[benzonb: 5,4-7]difuran-3,3'-啕哚]-2·(1Ή )-ketone; 3-[(2-keto-5,6-a wind snail [stupid-[l,2-b: 5,4-b'] s-puff _3,3'- ❹哚Η·(2Ή)-yl)methyl]tetrahydropyrrole-1-carboxylic acid third·butyl vinegar; (2S)-2-[(2·-keto-5,6-dihydrospiro[benzo [l,2-b : 5,4-b']diodor _3,3,_巧嗓]-1'(2Ή)-yl) fluorenyl] tetrahydro-p-r-u--1--acidic acid三丁丁酉; 4- [(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]disole _3 3L ρ引ρ朵] -Γ(2Ή)-yl)methyl]hexahydroguanidine-1-acidic acid third_丁自旨; 4'-gas-anthracene-{[5-(trifluoromethyl)oxime-2- Methyl bromide 5,6-dihydrospiro[benzo[l,2-b:5,4-b,]di-pyran-3,3'-呻嗓]-2'(1Ή)-one 4'-Gasyl-l'-[(2R)-tetrahydrofuran-2-ylmethyl]-5,6·dihydrospiro[benzo-2 b. 5,4-b']difuran-3 ,3,-啕哚]-2'(1Ή)-ketone; 143924-sp-20091127-6 •47- 201020257 4'-Momot-r-[(2R),hydrofuran-2-ylmethyl]_5 , 6_ dihydrospiro [benzo-like seven: 5.4- 1) '] difuran-3,3'-啕哚]-2'(1'11)-one; 1 -[4-(methylthio)爷]]-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3,-啕哚]-2'(1Ή)-one; 14( 2-methoxypyrimidin-5-yl)methyl]-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3'-吲哚] -2'(1Ή)-ketone; 71-carbyl-1'-((5-(trifluoromethyl)pyran-2-yl)indenyl)_5,6-dihydro-2-indole-spiro[benzo Furano[6,5-b]furan-3,3'-dihydrothromidium]-2'-one; (3R)-l'-(3-methylbutyl)-5,6-dihydrospiro [Benzo[i,2-b:5,4-b,]difuran-3,3,-吲哚]-2\1Ή)-one; (3 ft)-1'-pentyl-5,6 -Dihydrospiro[benzo[1,2-1):5,47']difuran-3,3,-4丨哚]-2\1Ή)-one; (3R)-r-(pyridine- 2-ylmethyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,5 丨哚]-2'(1Ή)-one ; (3R)-l-{[5-(two Fluoromethyl) pfluran-2-yl]fluorenyl}_5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-mouth 丨哚]-2,(1Ή)-ketone; (3S)-1·heptidin-2-ylindenyl)-5,6-dihydrospiro[benzo[l,2-b ··5,4_b, ]2 sniffing-3,3'-啕哚]-2'(1'11)-one; (3S)-l'-{[5-(trimethylmethyl)pyran-2-yl]methyl }-5,6-dihydrospiro[benzo: 5.4-b']difuran-3,3'-&lt;哚]-2'(1Ή)-one; 7'-gas-group-1'-[( Han)-tetrahydro cough-2-ylindenyl]-5,6-dihydrospiro [stupid 2_b: 5.4-b,] difuran-3,3,-啕哚]-2, (1Ή)- Ketone; 7'-fluoro-l'-[(2R)-rahydrofuran-2-ylindenyl]-5,6-dihydrospiro[plumbo[12-7:5.4-b']difuran-3 , 34丨哚]-2'(1Ή)-ketone; 143924-sp-20091127-6 -48- 201020257 4'-Fluoro-7--indenyl_r_[(2R)-tetrahydrofuran-2-ylmethyl J-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-啕哚]-2·(1Ή)-one; Γ-[2 -(2-methoxyethoxy)ethyl]_5,6-dihydrospiro[benzo[i,2_b: 5,4-b,]dioxan-3,3·-吲哚]-2 , (ΓΗ)-ketone; lH[(2S)-5-ketotetrahydropyrrole_2-yl]methyl b 5,6-dihydrospiro[benzo[U_b : 5.4- b] distiller -3-3,3·-啕哚]-2·(ΓΗ)-ketone; 1·-[2-(2-keto-1,3-tetrahydrocarbazole-3-yl)ethyl]_5,6 _ Dihydrospiro [Benzene like seven: 5.4- b'] Diterpenoid-3,3'-Qiao嗓]-2'(1Ή)-class; 1·-(4-Pyridin-2-ylindenyl)-5,6-dihydrospiro[benzo[i,2-b:5,4-7,]difuran_3,3·-吲哚]- 2 丫1Ή)-ketone; Γ-(' pyridine-2-ylf-yl)-5,6-dihydrospiro[benzo[u-b:5,4-b,]difuran-3,3,-吲哚]-2·(1Ή)-ketone; 1'-('Arid-4-ylindenyl)_5,6-dihydrospiro[benzonb: 5,4,7,difuran_3,3, _吲哚]-2\1Ή)-ketone; 1 -0»pyrylene-2-ylmethyl)-5,6-dihydrospiro[benzo[ub:5,4,7,]difuran-3, 3,-portion 哚]-2'(ΓΗ)-ketone; 14C7-fluoro-1-benzofuran-2-yl)methyl]_5,6-dihydrospiro[benzo[u_b: 5.4- b ']difuran-3,3'-吲哚]-2,(1,H)-one; Γ-(嗒耕-3-ylmercapto)-5,6-dihydrospiro[benzo[[ :5 4 7 1]difuran_3,3,-吲哚]-2'(1Ή)-one; 14(2-keto-1,3-tetrahydrocarbazole i-yl)methyl]5,6 _ Dihydrospiro[benzo[[7:5,47']difuran-3,3'-〃?丨哚]_2, (ι.Η)·ketone; 1 -[infraline oxy] lower group ]-5,6-dihydrospiro[benzo(10)7:5,472-furan_3 3,_吲哚]-2\ΓΗ)-ketone; 143924-sp-20091127-6 -49- 201020257 Γ- [(1-Methyl-1H-benzimidazol-2-yl)methyl]_5,6-dihydrospiro[ And [l,2-b: 5,4 seven'] 吱11南-3,3'-吲嗓]_2,(1,1*1)-鲷; Γ-(2Η-benzotrisole-2 -ylmethyl)_5,6-dihydrospiro[benzo-like seven:5,4-7,]difuran-3,3'-p?丨嗓]-2'(1Ή)-嗣; 2- [( 2'-keto-5,6-dihydrospiro[benzo[]L,2_b: 5,4-b,]difuran-3,3,-吲哚]-Γ(2Ή)-yl)methyl ] benzoic acid vinegar; 3- [(2'-keto-5,6-dihydrospiro[benzo[12_b:5,4-b,]difuran-3,3,-吲p]]Γ (2Ή)-yl)methyl]benzoic acid methyl vinegar; 4-[(2- yl-5,6-monohydrospiro[benzo[1,2-7:5,4-b']d-p-pentan -3,3,-M丨❹ 哚]-Γ(2Ή)-yl)methyl]benzoate oxime; 1-[3-(benzyloxy)propyl]-5,6-dihydrospiro[benzene And [!, 2_b : 5,4-b,] dipyran-3,3,-峋哚]-2'(ΓΗ)-ketone; 5-fluoro-1 -[(2R)-tetrahydrofuran_2_ Methyl]_5,6·dihydrospiro[benzo[^b : 5.4- b']dipyran-3,3'-吲嗓]-2'(l,H)-_ ; 6·-fluorine -l'-[(2R)-tetrahydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[u_b:5.4- b']dioxin-3,3'-吲,朵]- 2·(1Ή)-ketone; 1'-(hexahydro-p--4-ylmethyl&gt;5,6-dihydrospiro[benzo-like seven:5,4_b,]difur瘳-3,3·-啕哚]-2·(1Ή)-ketone; Γ-{[1-(1-mercaptoethyl)hexahydropyridine _4_yl] fluorenyl} 5,6·2 Hydrogen snail [benzo[l,2-b: 5,4-1»'] bicinch-3,3'-吲嗓]_2, (ΓΗ)-one; ethylhexahydropyridin-4-yl) Indenyl]_5,6-dihydrospiro[benzo[12-7:5 4 b,] difuran-3,3·-吲哚]-2Χ1Ή)-ketone hydrochloride; 14(1-methylhexahydro Pyridinyl)methyl]_5,6-dihydrospiro[benzo[u_b:5,4-7,]difuran-3,3'-吲哚]-indole(ΓΗ)-one; 143924-sp-20091127 -6 -50- 201020257 1 .)-tetrahydroindole $_2_ylmethyl]_5,6_dihydrospiro[benzoan b: 5 state difuran_3,3'-吲哚]_2, (ιή )-ketone; 31 steel-based-5,6-dihydrospiro [benzo[5:4,7]difurin_3 3, noise]-Γ(2Ή)-yl)methyl]benzoic acid; 1 -Η-[5-(Trifluoro->H,2,4_g二 4 _3·yl]-yl} 5,6-diaza snail [benzo[1'2-b. 5,4-7'] Furan-3,3'-W 哚]_2, (ι,η)-ketone; 1 [4 (5-methyl-1,2,4)-dioxazol-3-yl)-yl]5,6 Dichlorospiro[benzo[[:5,4-b']dioxin, 3,3'-noise]-2'(i,h)-one; ❹H(54 bite ice base ~~2· Methyl]-5,6-dihydrospiro[benzo[u_b: 5, 4_b,] difuran-3,3'-吲哚]-2'(l,H)-_ ; 1'-(4-峨-3-ylbenzyl)_5,6-dihydrospiro[benzo To suppress: 5 state difuran-^, _ 吲哚]-2'(1Ή)-ketone; 1 _[(2'-fluorobiphenyl-Φ-yl)methyl]_5 6_dihydrospiro[benzo Like seven: 5, 4 seven,] difuran-3,3'-啕哚]_2'(1Ή),; 1 [3-(5-methyl-1,2,4d all _3·yl) ]_5 6 di-spiral [benzo[(10): φ 5,4 seven'] difuran-3,3'-W 嗓]-2,(1Ή)-one; 1'-{3-[5-(three Fluoromethyl H, 2,4-oxadiazolungyl] aryl} 5 6 dihydrospiro [benzo[1'2-b : 5,4_b']difuran-3,3,-吲哚]- 2,(1'H)-ketone; Γ-[4-(5-methyl-4Η-1,2,4-tris-s--3-yl)-yl]-5 6-dihydrospiro[benzo[ : 5,47']difuran-3,3'-吲哚]_2'(1)-ketone; 2-[(2'-keto-5,6-dihydrospiro[benzo[u_b: 5,4 bi]difuran_3,3·(5) 哚]-1·(2Ή)-yl)methyl]benzoic acid; 4-[(2,-keto-5,6-dihydrospiro[benzo [u_b : Μ7,]difuran _3,3, 巧哚]-Γ(2·Η)-yl)methyl] benzoic acid; 143924-sp-20091127-6 •51 - 201020257 Γ-(3-hydroxy Propyl)-5,6-dihydrospiro[benzo[12_b:5,4-b']difuran_3,n哚]-2'(1Ή)-ketone; 2'-keto-1'-[(21〇-tetrahydrofuran-2-ylmethyl]-1',2,,5,6-tetrahydrospiro[benzo [l,2-b : 5,4-b']difuran-3,3'-吲哚]_4,_phthalonitrile; 2'-keto-l'-[(2R)-tetrahydrofuran-2-yl Methyl ^, ^ Bu tetrahydrospiro and [1,2-b : 5,4-b'] dimethane-3,3'-叼丨ρ flower]-4'-rebel formic acid; 4'- [(Dimethylamino)methyl]-r-[(2R)-izghydrofuran-2-ylmethyl]_5,6-dihydrospiro[benzo[l,2-b: 5,4-b ']二吱》南丨嗓]-2,(1Ή)-_ ; 4·-(tetrahydropyrrol-1-ylmethyl)-l'-[(2R)_tetrahydrofuran-2-ylmethyl]5 ,6 dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3,-anthracene-2,(1Ή)-one; 4'-amino-1' -[(21〇-tetrahydrofuran-2-ylindenyl]_5,6-dihydrospiro[benzo-like seven: 5.4-b']difuran-3,3'-啕哚]々'(ΓΗ)-ketone ; Γ-(morpholine-2-ylmethyl)-5,6-dihydrospiro[benzo-like seven:5,4,7,]difuran_3,3,_峋哚]-2' (1Ή )-ketone; 1'-[(4-methyl-wufolin-2-yl)methyl]-5,6-dihydrospiro[benzo[i,2_b:5,4-b']difuran- 3,3W Budu]-2'(1Ή)-net; 1 -{[4-(1-mercaptoethyl)norfosine_2_yl]methyl 5,6-dihydrospiro[benzo[i,2_b : 5.4- b]difuran-3,3'-吲哚]-2·(1Ή)-one; 1-methyl-5,6-monohydrogen Snail [benzo[i,2-b: 5,4-1&gt;'] dim--3,3,-&lt;»5丨嗓]-2,(1Ή)_ ketone; 1 -[4-( 1Η-tetras-5-yl) Yuji]-5,6-dihydrospiro[benzo[i,2_b : 5,4-b']dioxan-3,3'-吲哚]-2' (1Ή)-_ ; 1'-(3-Goldyl)-5,6-dihydrospiro[benzo[i,2-b : 5,4-b,]dipyran-3,3,-啕哚]-2\ΓΗ)-ketone; 143924-sp-20091127-6 -52· 201020257 Γ-(4-fosfolininyl)_5,6-dihydrospiro[benzo-5,4 b, Difuran-3,3'-吲哚]_2, (1Ή)-one; 1'-(tetrahydroindol-3-ylmethyl)-5,6-dihydrospiro[benzo[u_b: 5 4,7,]difuran-3,3,吲哚]々'(ΓΗ)-one; N-(l-mercaptoethyl)_3-[(2'-keto-5,6-dihydrospiro[ Benzene like seven: 5,4_b]difuran-3,3'-吲哚]·ι'(2Ή)-yl)methyl]tetrahydropyrrole hydrazide; (3S)-1'-[(2R )-tetrahydroindolizine_2_ylmethyl]-5,6-dihydrospiro[benzo[[7:5,4-7,]difuran-3,3W丨哚]-2'(1Ή)- Ketone; ^(3R)I[(2R)_1Z9 hydrogen PH2_yl f-group]_5,6·dihydrospiro[benzo[l,2-b: 5,4-b1 Furan-3,3.5 丨哚]-2'(1Ή)-one; (3R)-l'-[(2S)-izghydrofuran-2-ylmethyl]-5,6-dihydrospiro[ Benzo[[7:5,47'] difuran-3,3'-&lt;哚]-2丫1Ή)-one; (3S)-1'-[(2S)-tetrahydrofuran-2-yl ]]-5,6-dihydrospiro[benzo[[7:5 4_brj difuran-3,3. 5 b]-2"(1'11)-one; 1 -{[(2S)-1 -Methyl-5--yltetraiso-p-pyridin-2-yl]hydrazinobu 5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3, 3·-哚哚]-2'(1Ή)·ketone; Ν-(cyclohexylmethyl)-3-[(2'-fluorenyl-5,6-dihydrospiro[benzo[1,2-7: 5,4-b']dipyran-3,3'-吲哚]-1·(2Ή&gt;yl)methyl]benzamide; Ν-(2-methoxyethyl)-3-[ (2'-keto-5,6-dihydrospiro[benzo[7:5,4-b']difuran-3,3'-indole]-indole (2Ή)-yl)indenyl]benzene Mercaptoamine; Ν-hexyl-fluorenyl-mercapto-3-[(2'-keto-5,6-dihydrospiro[benzo[^,7:5,4-b']dioxan- 3,3'-thirty 哚]-Γ(2Ή)-yl)methyl]benzamide; Ν-(2-ethylbutyl)-3-[(2'-fluorenyl-5,6-di Hydrogen snail [benzo[i,2_b: 5,4-b·]d ρ 矢0南-3,3'-嗍哚]-Γ(2Ή)-yl)methyl]benzoguanamine; 143924-sp -20091127- 6-53- 201020257 N-(2,4-Dimercaptophenyl)-3-[(2'-keto-5,6-dihydrospiro[benzo[ub:5,4-b·]) Furan-3,3'-吲哚]-1'(2Ή)-yl)indolyl]phenylhydrazine; 3-[(2'-keto-5,6-dihydrospiro[benzo[l, 2-b : 5,4-b,]difuran-3,3,- 4 哚]-Γ(2Ή)-yl)indenyl]-N-(2-phenylpropyl)benzoguanamine; N -[(1S)-1-cyclohexylethyl]-3-[(2'--yl-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran) -3,3'-吲哚]-Γ(2Ή)-yl)methyl]phenyl hydrazide; N-[(1R)-1-cyclohexylethyl]-3-[(2'-keto- 5,6-dihydrospiro[benzo[i,2-b:5,4-b]difuran-3,3M丨哚]-indole (2Ή)-yl)methyl]benzamide; (4-ethylphenyl)-2-[(2·-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-b,]difuran-3,3^吲哚]-1\2 only)-yl) fluorenyl]benzamide; N-(2-ethylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzene And [7:5,4,7,]difuran-3,3'-thoracic]-indole (2Ή)-yl)indolyl]benzamine; Ν-(2,4-dimercaptophenyl) )-2-[(2'-keto-5,6-dihydrospiro[benzo[7:5,4-b']difuran-3,3'-(9)哚]-1'(2Ή) -yl)methyl]benzamide Ν-(2-methoxyphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzoHb: 5,4-b']difuran-3,3,-沔丨Mouth]-1,(2Ή)-yl)methyl] benzoate; Ν-(2-phenylphenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo [i,2-b : 5,4-b']二吱0南-3,3'-called I嗓]-1'(2Ή)-yl)methyl]benzoquinone; Phenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[1,2:7:5,4-1)]2 bite 0 South_3,3,___ -1'(2Ή)-yl)methyl]benzoquinone; Ν-(3-fluoro-2-indenylphenyl)-2-[(2·-keto-5,6-dihydrospiro) [Benzo[i,2-b: 5,4-b']difuran-3,3'-吲哚]-indole (2Ή)-yl)indenyl]benzamide; Ν-heptyl-2 -[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-1&gt;'] dip-pentan-3,3'-ρ5丨哚]-Γ (2Ή)-yl)methyl]benzamide; 143924-SD-20091127-6 -54- 201020257 N-(2-abenzyl)-2-[(2'-keto-5,6-di Hydrogen snail [benzo[1,2:7:5,4-b,] two biting -3,3'-吲哚]-Γ(2Ή)-yl) fluorenyl] alum; amine amine; 2-(hexahydropyridin-1-ylcarbonyl)-yl]-5,6-dihydrospiro[benzo[12_b:5,4-b,]difuran-3,3'-吲哚]-2' (1Ή)-ketone; Ν- Butyl-2-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']di-n--3,3'-θ丨哚Η ·(2Ή)-yl)methyl]benzamide; Ν-(3-methylphenyl)-2-[(2·-keto-5,6-dihydrospiro[benzo[1,2 7:5,4-b']dipyran-3,3'-啕哚]-1'(2Ή)-yl)mercapto]benzamide; ® Ν-(2-fluoro-5-- Phenyl)-2-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b: 5,4-7,]difuran-3,3,5丨哚]- Γ(2Ή)-yl)methyl]phenyl hydrazide; Ν-(2,3-dimercaptophenyl)-2-[(2'-_ yl-5,6-dihydro snail [stupid [ ι,27:5,4-b']difuran-33-呻哚]-Γ(2Ή)-yl)indolyl]benzamine; Ν-[2-(4-曱-oxyphenyl) ]]-2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b·] diterpene-3,3·-»5 ]-1'(2Ή)-yl)methyl]benzoquinone; Ν-(3-carbobenzyl)-2-[(2'-keto-5,6-dihydrospiro[stuppy[U 7:5,4_b,]difuran-3,3'-啕哚]-Γ(2Ή)-yl)indolyl]phenylhydrazine; Ν-[2-(4-phenylphenyl)ethyl]- 2-[(2·-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3·-蚓哚]-Γ(2Ή) -yl)methyl]benzamide; Ν-(2-曱Phenyl)-4-[(2'-keto-5,6-dihydrospiro[benzox,2:7:5,4?|]difuran_3,3'-吲哚]-Γ(2Ή )-yl)methyl]benzamide; 4-[(Τ-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difurene-3 ,3,- W 哚]-Γ(2Ή)-yl) fluorenyl]-N-[2-(trifluoromethyl)phenyl]benzamide; 4-[(2·-keto-5, 6-Dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3,-啕哚]-indole (2Ή)-yl)methyl]-N-phenylbenzene Methionamine; 143924-sp-20091127-6 • 55· 201020257 N-methyl-4-[(2,-keto-5,6-dihydrospiro[benzo-like seven:5,4-7,] two Furan_3,3,_pb丨p]-Γ(2'Η)-yl)mercapto]benzoquinone; Ν-(2-fluorophenyl)-4-[(2'-keto- 5,6-dihydrospiro[benzo[12-7:5 4,7]difuran-3,3'-吲哚Η'(2Ή)-yl)indolyl]benzoquinone; 4-[(2 '-keto-5,6-dihydrospiro[benzo[^7:5,4_b,]difuran·3,3,_ 丨哚 丨哚]-1 (2Ή)-yl)methyl]-Ν- (2-喽-phen-2-ylethyl)phenylhydrazine; 4-[(2'- _yl-5,6-dihydrospiro[benzo-like seven:5,4 b,]difuran_3 ,3,_吲哚Η'(2Ή)-yl)methyl]benzamide; Ν-(2,3-dihydro- 1Η-茚-5-yl)-4-[(2'-keto_5,6-dihydrospiro[benzo[l,2-b: 5,4-b,]difuran-3,3W丨哚]-Γ(2'Η)-yl)methyl]phenyl hydrazide; Γ-[4-(huffolin-4-ylcarbonyl) aryl]_5,6-dihydro snail [stupid [1] , 2:7,5,4,7,]difuran-3,34丨哚]-2'(1Ή)-one; Ν-(2-ethylphenyl)-4-[(2'-keto-5) ,6-dihydrospiro[benzo(1) from:5,4_b,]difuran-3,3'-吲哚Η'(2Ή)-yl)methyl]benzamide; Ν-(2,6- Dimethylphenyl)-4-[(2·-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']difuran-3,3·-吲哚]-Γ(2Ή)-yl) fluorenyl]benzamine; Ν-(3-fluorophenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo-like :5,4-b']difuran-3,3% 丨哚丨哚]-1'(2Ή)-yl)methyl]phenyl hydrazide; Ν-(2,4-dimercaptophenyl)- 4-[(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b,]difuran-3,3'-吲哚]-1' (2Ή )-yl)methyl]benzoquinone; 4-[(2'--yl-5,6-dihydrospiro[benzo[l,2-b: 5,4-b'] ρ odor -3,3,-〃?丨11 ]]-1'(2Ή)-yl) fluorenyl]-N-decone-2-ylindenyl) benzoquinone; Ν-ethyl-4-[ (2'- -5,6-dihydrospiro[benzo[i,2-b:5,4-b']dioxan]-indole (2Ή)-yl)methyl]phenyl hydrazide; 143924- Sp-20091127-6 •56- 201020257 N-(2-methoxyethyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5, 4-b']difuran-3,3·-吲哚]-1'(2Ή)-yl)methyl]phenylhydrazine; Ν-(2-ethoxyethyl) hopper [(2·- Keto-5,6-dihydrospiro[benzo[l,2-b: 5,4-b']difuran-3,3·-吲哚]-1'(2Ή)-yl)methyl] Phenylamine; 1^-cyclobutyl-4-[(2-keto-5,6-dihydrospiro[benzo[1,2-1»:5,47'] dipyran-3 , 3-吲哚]-1(2Η)-yl) fluorenyl]benzamide; 4-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b: 5 , 4,7,]difuran-3,3,-吲哚]-1'(2Ή)-yl)indolyl]-Nl,3-p-conazole-2-ylbenzimidamide; ® \-(3 -fluoro-2-methylphenyl)-4-[(2'-keto-5,6-dihydrospiro[benzo[1,2-7:5,4-7'] difuran-3,3 ·-吲哚Η'(2Ή)-yl)methyl]benzamide; Ν-(2-ethylbutyl)-4-[(2'-keto-5,6-dihydrospiro[benzene And [l,2-b: 5,4-b]difuran-3,3·-(4)哚]-Γ(2Ή)-yl)indolyl]benzamide; 2-(2·-keto- 5,6-dihydrospiro[ Benzo[l,2-b:5,4-b']di-p-pentan-3,3'- ρ?ί 哚]-Γ(2Ή)-yl)acetamide; Ν-(4-ethyl Phenyl)-2-(2'-keto-5,6-dihydrospiro[benzo[i,2-b:5,4-b']di-puffin-3,3'-嘀哚] -1乂2)-yl)acetamide; 乂!^-diethyl-2-(2'-keto-5,6-dihydrospiro[benzo[1,2-13:5,4 -1),]二吱'1南-3,3'-啕哚]-Γ(2Ή)-yl)acetamide; team (3,3-dimercaptobutyl)-2-(2·- Reticyl-5,6-dihydrospiro[benzo[1,2-7:5,4-7']difuran-3,3'-吲哚]-1'(2Ή)-yl)acetamide; N -[3-(l-methylethoxy)propyl]-2-(2'-keto-5,6-dihydrospiro[benzo[ub:5,4-b']difuran-3 ,3,-吲哚]-1, (2Ή&gt; group) acetamidine; 2-(2'-keto-5,6-di-argon snail [benzo[l,2-b: 5,4-b ']二吱喃-3,3,-沔| 哚]-Γ(2Ή)-yl)-N-propylacetamide; 143924-sp-20091127-6 •57· 201020257 N-methyl-2- (2-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b']diolol 0--3,3Ί 哚]-1'(2Ή)-yl)- Ν-phenylacetamide; Ν-(2,5-methylphenyl)-2-(2'-keto-5,6-dihydrospiro[stuppy[1,2:7:5,4 -b,]difuran-3,3'-吲哚]-1' (2 Ή)-yl) acetamidine; Ν-(2,4-mercaptophenyl)-2-(2'-keto-5,6-dihydrospiro[benzopyrene, 2:7:5,4 -1),]difuran-3,3'-吲哚]-fluorene (2Ή)-yl)acetamide; Ν-(2,3-dimercaptophenyl)-2-(2'-keto -5,6-dihydrospiro[benzo[[7:5,4-b']difuran-3,3'-吲哚]-indole (2Ή)-yl)acetamide; Ν-(2, 6-Dimethylphenyl)-2-(2·-keto-5,6-dihydrospiro[benzo[u_b : 5,4_b,]difuran-3,3'-吲哚]-Γ( 2Ή)-yl)acetamide; 5-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]diterpene-3,3 ·-嘀哚]-Γ(2Ή)-yl)methyl]furan-2-carboxylic acid; Ν,Ν-dimercapto-5-[(2·-keto-5,6-dihydrospiro[benzene] And [7:5,4_b,]difuran-3J-吲哚]-1'(2Ή)-yl)methyl]-ranyl-2-carboxamide; Ν-methyl-5-[(2' -keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]dioxin-3,3,-啕哚]-Γ(2Ή)-yl) fluorenyl Furan-2-carboxyguanamine; 2-[(2'-keto-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]dioxan-3,3 ,-峋哚]-1·(2Ή)-yl)methyl]-1,3-oxazol-4-carboxyindoleamine, N,N-dimercapto-2-[(2'-keto- 5,6-dihydrospiro[benzo[l,2-b : 5,4-b·]difuran-3,3'-p5丨p]-1'(2Ή)-yl)indolyl]-1,3-&lt;» 吐-4- acrolein; 14(2S)-2-hydroxypropyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b.]difuran-3,3·-啕哚]-2· (1Ή)-ketone; 14(25)-2-(benzyloxy)propyl]-5,6-dihydrospiro[benzo[1,2-7:5,4-7']difuran-3,3 '-啕哚] ketone; 143924-SD-20091127-6 -58- 201020257 l'-{(2S)-2-[(4-fluorobenzyl)oxy]propyl}-5,6-dihydrospiro [Benzo[i,2-b:5,4-b.]difuran-3,3'-thrhhd]-2丫ΓΗ)-one; 14(2S)-2-(pyridin-2-yl)曱oxy)propyl]-5,6-dihydrospiro[benzo[i,2-b: 5,4-b']difuran-3,3'-峋哚]-2'(1Ή)- Ketone; 1·-(3-hydroxybutyl)-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]dioxan-3,3,-clear]- 2'(1Ή)-ketone; Γ-(4,4,4-trifluoro-3-hydroxybutyl)-5,6-dihydrospiro[benzo[1,2:7:5,4-b,] Difuroline-3,3'-indole]-2'(1Ή)-one; ® 3-(2'-keto-5,6-diindole [benzo[l,2-b: 5, 4-b']diazol-3Χ 嗓]-Γ(2Ή)-yl)propanal; Γ-{3-[(3-methylbutyl)amino]propyl}-5,6-dihydro Snail [benzo[i,2-b : 5,4-b,]difuran-3,3' - 哚 哚]-2'(1Ή)-keto hydrochloride; [butyl(methyl)amino]propyl}-5,6-dihydrospiro[benzo[i,2-b: 5,4 -b,] Two bite -3,3.丨哚]-2'(1 ah)-ketohydrochloride; 143-[(2,2,2-trifluoroethyl)amino]propyl}·5,6-dihydrospiro [stupid [ i,2-b: 5,4-b,]difuran-3,3'-indole]-2'(1Ή)-one hydrochloride; 3-{[3-(2'-mercapto-5 ,6-dihydrospiro[benzo[l,2-b:5,4-b']dioxan-3,3·-ρ?1 嗓Η'(2Ή)-yl)propyl]amino} Propionitrile hydrochloride; 446-(diguanylamino)pyridine_3_yl H'_[(2R)_tetrahydrofuran-2-ylmethyl]·%-dihydrospiro[benzo[l,2-b : 5,4-b']difuran-3,3,-啕哚]-2'(1Ή)-one; 4'-[(E)_2-(4-fluorophenyl)vinyl]-14( 2R)-W-hydrofuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-7']difuran-3,3'-吲哚]-2 '(1Ή)-keto; 4'-dibenzo[b,d]porphin-4-yl-1,-[(2-p-tetrahydrofuran-2-ylmethyl)_5,6-dihydrospiro[benzene And [l,2-b: 5,4-b']difuran-3,3·-吲哚]-2,(1Ή)-one; 143924-sp-2009l 127-6 -59- 201020257 4_(1 -Benzophenophen-3-yl)-l'-[(2R)-tetrahydroindolyl-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b: 5 , 4-b']difuran-3,3'-吲哚]-2' (1 condition)-ketone; 4'-(1-indolyl-1H-indol-5-yl)-r-[( 2R)-tetrahydrofuran-2-ylmethyl]-5,6 - 二气螺[笨和[l,2-b : 5,4-b']difuran-3,3.? Budu]-2·(1Ή)-one; 4'-[3,5-double (trifluoromethyl)phenyl]arfuran-2-ylmethyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b']difuran-3,3' -啕哚]-2·(1Ή)-one; 4'_(4-phenoxyphenyl)-1'-[(21〇-tetrahydrofuran-2-ylindenyl]-5,6-dihydrospiro [Stupid [l,2-b: 5,4-b·]difuran-3,3'-吲哚]-2,(1Ή)-one; 4'-[4-(2-methylpropoxy) Phenyl]_14(2R)_tetrahydrofuran_2_ylindenyl]_5 6_dihydrospiro[benzo[l,2-b : 5,4-b']difuran-3,3·-(9)哚]-2·(1Ή)-ketone; 4'-(4-butoxyphenyltetrahydrofuran-2-ylmethyl]-5,6-dihydrospiro [stupid [l,2-b: 5, 4,7,]difuran-3,3,-吲哚]-2,(1Ή)-one; 4-(4-methylphenyl)_1'_[(2 ft)-tetrahydroanthracene _2 -ylindolyl]-5,6-dihydrospiro[benzo[l,2-b:5,4-b,]difuran-3,3'-indole]-2,(1Ή)-one; 4·-pyrimidin-5-yl-l'-[(2R&gt;rahydrofuran-2-ylindolyl]-5,6-dihydrospiro[benzo[l,2-b: 5,4-b, Dimethane-3,3·-嘀哚]-2,(1Ή)-one; and 4-[6-(diamidoamine) bite_3-yl]_ι·_{[5·(three Fluoromethyl) 2-yl] fluorenyl 5,6-di-spiro[benzo[i,2-b:5,4-b']dioxin-3,3'-&lt;»5丨嗓]-2' (1Ή)-ketooxime (two abbreviated)-2',3·,5,6-tetrahydrospiro [benzo-like seven:5,4-7,]difuran-3,841,4] Dioxetene And [2,3-f]吲哚]-7,(6Ή)-one; 3'_(4-decyloxyindenyl)-5,6-dihydrospiro[benzox,2-b: 5 ,4-b,]difuran_3,1,_峨-[3,2-f]quinoline]-2,(3Ή)-one; 2',3',5,6-tetrahydrospiro[ Benzo[1,2:7,5,4,7,2,2,8,-[1,4]dioxanthene and [2,3〇啕哚]-7'(6Ή)-鲷; 143924-sp-20091127-6 60· 201020257 1 -[4-(lowoxy)indolyl]-5,6-dihydrospiro[benzo:5,4-15]difuran-3,3,-哚 哚]-2Χ1Ή)-ketone; 2 2 2,-keto-based dihydrospiro[benzo-[:54 VII]difuran m 嗓]-1(211)-yl)propyl]]11_isoindole哚_1,3 (Liaodione; 1-(3-aminopropyl)-5,6-dihydrospiro[stupid [to seven:5,4-7,]difuran_3,3,_吲哚]-2'(1Ή)-ketone; Ν-[3-(2-mercapto-5,6-dihydrospiro[benzo:5,4?']difuran_3,3,_吲ρ木]-1 (2H)-yl)propyl]_2-(trifluoromethoxy)phenylguanamine; or β 1-(4-oxindole) Base)-5,6-dihydrospiro [stupidyl 27:5,4b,]difuran_3,3,_吲 哚]-2'(1Ή)-one. 13. The compound of claim 1 wherein L is Ch2 - and Μ is _〇_. 14. A compound according to claim 13 which is selected from the group consisting of: 1 'decapine-2-ylindenyl)-6,7-dihydrospiro[benzox,2_b:4,5-b,]difuran -3,3W丨哚]-2'(1Ή)-ketone; 14(21〇-tetrahydrofuran-2-ylindenyl]-6J-dihydrospiro[benzo[i,2-b : 4,5-b1 Difuroyl-3,3'-峋哚]-2·(1Ή)-one; or r-[(2R)-l,4-dioxoindolin-2-ylmethyl]-6,7 - Dihydrospiro[benzo[1,2-b:4,5-b,]difuran-3,3'-啕哚]-2'(1Ή)-one. 15.-Formula (IV) compound : Wherein: q is 1, 2 or 3; 143924-sp.20091127-6 -61- 201020257 R7 is hydrogen, (5-aero-2-pyranyl)methyl, 2-(2-methoxyethoxy) Ethyl, di-p-methyl, 4-decyloxybenzyl, 3-mercaptobutyl, decyl, 4-bromo-based, 2,3-dihydro-1,4-benzodiox Terpene _6-ylmethyl, 2-(trifluoromethyl)-yl, [3-(trifluoromethyl)acridin-2-yl]methyl, [5-(yloxy)P-pyridyl -2-yl]methyl'hexahydropyridinyl hydrazino, (1-methylhexahydropyridyl)methyl, (5-pyridylpyridin-2-yl)methyl, [5-(trifluoro Methyl)furan-2-yl]methyl'(2R)-tetrahydrofuran-2-ylmethyl, pyridin-2-ylmethyl, pyridin-3-ylindenyl, tetrahydro-2H-pyran-4- Methyl, tetrahydro-2H-piperidin-2-ylmethyl '[1-(tris-butoxycarbonyl)hexahydropyridyl-4-yl]methyl, 4_[(3R)tetrahydro-? Abbreviated as a hydrogen, a hydroxy group, a bromine group, a gas group, a cyano group, a fluoro group, Methyl, difluoroacetinyl, methoxy, μmethylethoxy, 2-methoxyethoxy, +oxy 1_(second-butoxy Tetrahydropyrheptin-3-yloxy, tetrahydrofuroyl-3-yloxy, amine, sulfonylamino, methanesulfonylamino, [(t-butoxycarbonyl)tetra Hydropyrrolidinyl]amino, 6-methoxypyridine, 5-methyl 4,2,4-indenyldipyridyl, amine (imido)indolyl or (tetrahydropyrrole-3 - Alkyl; hydrazine or two R8 groups and the adjacent carbon to which they are attached - form a fused dioxyterpene ring, a fused thiophene ring, fused U-dione-based porphinyl ring, fused u, 5-oxadiazolyl ring fused fused tetrahydropyranyl ring, fused 2,3-dihydropyrrepsyl ring Slightly combined with &amp; methyl-4,5-dihydroisoxazolyl ring or fused pyridyl ring, and the R8 group, if present, is as described above; Or a pharmaceutically acceptable salt, solvate or prodrug thereof; 143924-sp-20091127-6-62.201020257. 16. The compound of claim 15, which is selected from the group consisting of: 1 - deuterium. Ding-2-ylmethyl) snail [吱 并[2 3 g] quinoxaline _8,3Lp?丨哚]_2, (1Ή) ketone; 1_(monophenylmethyl) snail (tetra) 哚-3, 3,^塞吩和[2,3那]benzofuran]-2(1Η)-one; 1_(monophenylmethyl)spiro(tetra)indole-3,3'_嗓-[2,3-f] [l]benzofuran]-2(1Η)-keto 5,5'-dioxide; spirulina-3,3'-ρseno[2,3-f][i]benzo Furan]_2(1Η)__ 5,5,_dioxide; or 1-0 than bit-2-yl indenyl) snail [called 丨哚3,3L 喽-[2,3 f](1) benzene And furan]-2(1H)-one 5,5'-dioxide; 1 oxime benzyl)_3_indolyl snail [snolo[2,3-f][l,2]benzo Isoxazole-7,3,-吲哚]-2·(ΓΗ)-one; '5_(yloxy)-Γ-[(5-chloro-2-pyrimenyl)methyl] snail [μ Benzofuran_3,3,·吲哚]-2'(ΓΗ)-_ ; φ 1_(diphenylmethyl)-6-methoxy-5-methylspiro[1-benzofuran-3, 3,-吲哚]-2,(1,Η)-ketone; 6-,/odoryl-indole-(diphenylmethyl)spiro[ι_benzofuran_3 3,_吲哚]_2, ( 1Ή) ketone; Γ-(diphenylfluorenyl)-5,6-dimethylspiro[1-benzofuran-3,3,-thirsty]-2'(1Ή)-one; 6_(oxyl )-Γ-(diphenylmethyl)spiro[1-benzofuran_3,3,-吲哚]-2 , (1Ή)-ketone; Γ-(diphenylmethyl)-5-fluoro-6-methoxyspiro[μbenzofuran_3,3'_啕哚]_ 2'(1Ή)-one; 1'-(diphenylfluorenyl)-5-1ylspiro[1-benzofuran-3,3·-吲哚]-Τα'Η)-one; 1'-(diphenylfluorenyl)-6-曱oxyspiro[1-benzofuran-3,3',哚]-2'(1Ή)-one; 143924-sp-20091127-6 -63. 201020257 6-(benzyloxy)-l'-( 3-methylbutyl)spirofl_benzofuran-3,3,-β哚]-2,(1Ή)-one; 6-glyme-Γ-{[5-(trifluoromethyl)anthran _2_yl]methyl}spiro[^benzofuran_3,3,_吲哚]-2'(1Ή)-one; 5-glycol-1'-{[5-(trifluoromethyl)吱 · 2 2 2 ] ] 2 2 2 2 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 苯 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 6 3,3,_(4)哚]_2,(1Ή)_one; 6-bromospiro[1-benzofuran_3,3,_吲哚]_2,(1Ή)-one; 5,6-dimethyl Snail [1-benzofuran_3,3·_^ 哚]_2ι(1Ή)__ ; 5-fluoro-6-methoxyspiro[1-benzofuran_3,3,_峋哚;|_2 , (ι,Η)-ketone; 5-fluoro-spiro[1-benzopyran-3,3'-吲嗓]-2,(1Ή)-one; 6-decyloxyspiro[1-benzo Furan _3,3,- 哚 哚]-2,(1Ή)-one; 6- Spiro [1-ρ-fu thiopyran _3,3, indole throat _] _2, (1Ή) - one; l - (diphenyl Yue-yl) -6 via spiro [benzo 1_ squeak. South _3,3Ί嗓]_2'(1Ή)-ketone; 3-{[Γ-(diphenylmethyl)-1-keto-1,2,-dihydrospiro[1-benzofuran_3, 3'-noise] winter base] oxy} tetrahydro ρ ratio η each___ retinoic acid third-butyl ester; 3-[(2'-keto-1',2'-dihydrospiro[1 _Benzoindole _33,, 嗓]yl)oxy]tetrahydrofuran-1-carboxylic acid tert-butyl ester; (3S)-6·decyloxy-5-methyl snail [1- Benzofuran_3,3,_w哚]_2,(1Ή)-one; (3R)-6-decyloxy-5-methylspiro[1-benzofuran_3,3,-峋哚]_2 ,(ΓΗ)-ketone; 6-methoxy-5-methyl-l'-[(2R)-®hydrofuran_2_ylindenyl]spiro[1-benzofuran-3,3'-W哚]-2'(rH)-one; 6-methoxy-5-mercapto-1,-(pyridine_2-ylindenyl)spiro[μbenzofuran_3,3,_吲哚]- 2'(1Ή)-one; 6-decyloxy-5-methyl-1·-(tetrahydro-2-indole-piperidin-2-ylmethyl)spiro[1-benzofuran 143924-sp-20091127- 6 -64- 201020257 -3,3,-啕哚]-2'(1Ή)-ketone; 5-fluoro-6-methoxy-indole-(tetrahydro-2-indole-piperidin-2-ylmethyl) Spirulina fl_benzofuran-3,3%5 丨哚]-2'(1Ή)-one; 5-fractyl-6-methoxy-indole-(峨方-2-ylmethyl-μ[ μ 并 and furan-3,3,_ρ 哚]-Ζ(1Ή)-ketone; 5-fluoro-6-methoxy-r-[(2R)-®hydrofuran-2-ylindenyl] snail [ι_benzopyrene-3,3'-啕哚]-2·(ΓΗ )-ketone; 1_mercapto-5-fluoro-6-anthracene snail [1- 弁 弁 _3,3'-&gt;»5 卜 ]]_2, (ι·η)-_ ; ® 6_曱oxy-l'-[(2R)_tetrahydrofuran-2-ylindenyl]spiro[1-benzofuran_3,3,_吲哚]-2'(γη)-one; 6- Bromo-r-[(2R)-w-hydrofuran-2-ylmethyl]spirobenzofuran-33, hydrazine]-2'(1Ή)-one; 6-fluoro-5-methoxy- Γ-{[5-(Trifluoromethyl)pyran-2-yl]methyl}spiro[1·benzofuran-3,3'-吲哚]-Ζ(ΓΗ)-one; 5.6-dimethyl Γ-Γ-(tetrahydro-2-indole-piperidin-2-ylmethyl)spiro[1-benzofuran_3,3'_&lt;哚]-2'(1Ή)-one; 5.6-dimethyl- Γ-(tetrahydro-2-indole-piperazin-4-ylmethyl)spiro[1-benzofuran_3,3,4丨哚]-2'(indenyl)-one; 5.6-dimercapto-14pyridine -2-ylindenyl)spiro[1-benzofuran-3,3'-吲哚]-2\1 ugly)-ketone; 5-fluoro-6-methoxy-indole-(tetrahydro-2-indole) -piperazin-4-ylindenyl)spiro[1-benzofuran-3,3'-oxime]-2'(1Ή)-one; 5-fluoro-6-methoxy-oxime-{[ 5-(Trifluoromethyl)furan-2-yl]methyl}spiro[1-benzofuran-3,3'-吲哚]-2' (1 Ή)-ketone; 143924-sp-20091127-6 -65· 201020257 5.6-difluoro-indole-(pyridin-3-ylmethyl)spiro[1-benzofuran_3,3,-吲哚]-2 , (1Ή)-keto; 5.6-difluoro-1'-{[5-(trifluoromethyl) oxime-2-yl]methyl} snail [1- benzopyran-3,3'-啕哚]-2'(ΓΗ)-ketone; 6-methoxy-oxime-(pyridin-2-ylmethyl) snail [1- benzofuran-3,3'-啕哚]-2'(1Ή) - ketone; 6-methoxy-indole-(pyridin-3-ylmethyl)spiro[1-indolofuran-3,3'-吲哚]-2,(1Ή)-one; 6-decyloxy -Γ-(tetrahydro-2Η-piperazin-4-ylindenyl)spiro[1-benzofuran-3,3,-吲哚]-2'(1Ή)-one; 6-methoxy-oxime -(tetrahydro-2-indole-piperidin-2-ylindenyl)spiro[1-benzofuran-3,3,-indole]-2'(1Ή)-one; 6-amino-14(2R) -tetrahydrofuran-2-ylindenyl]spiro[1-benzofuran_3,3,_啕哚]-2'(1Ή)-one; Ν-{2·-keto-l'-[(2R) -tetrahydrofuran-2-ylindenyl η',2,-dihydrospiro[1-benzofuran-3,3'-吲哚]-6-yl}nonanesulfonamide; 6-hydroxy-indole-( 3-methylbutyl)spiro[1-benzopyrano_3,3,_decade]-2,(1Ή)-one; 6-hydroxy-l'-(3-mercaptobutyl)_5- (trifluoroethenyl) snail [] L•benzofuran _3, 3, _Ρ弓丨哚]-2'(ΓΗ)-ketone; (3R)-3-[(2·-keto-oxime-{[5-(tri-I-yl)pyran-2-yl]- Keb r, 2'-dihydrospiro[1-benzofuran-3,3^吲哚]-6-yl)amino]tetrahydropyrrole small carboxylic acid tert-butyl ester; 6-[(3R) -tetrahydropyrrol-3-ylamino]-indole, -{[5-(trifluoromethyl)pyran-2-yl]methyl} spiro[1-benzofuran-3,3'-吲哚]-2'(1Ή)-ketone; 143924-sp-20091127-6 -66- 201020257 6-hydroxy-r-[(2R)-E3hydrofuran-2-ylmethyl]spirobenzofuran-33,哚]-2'(1Ή)-ketone; 6-(1-methylethoxy)-1'-[(21〇-tetrahydrofuran-2-ylmethyl] snail [1_ benzofurazan-3 , 3'-峋哚]-2'(1Ή)-ketone; (3S)-3_({2·-keto-l'-[(2R)-rahydrofuran_2_ylindenyl dioxo Stupid and sulphur-3,3'-啕嗓]-6-yl}oxy)tetrahydropyrrole small resorcinic acid third. 6-[(3S)-tetrahydropyrrole-3-yloxy]-l, -[(2R)-tetrahydrofuran-2-ylmethyl]-spiro-benzopyran--3,3[noisex]-2\1Ή)-yl hydrochloride; (3R)-3-({2'-keto-l'-[(2R)-tetrahydrofuran-2-ylmethyl η',2,-dihydrospiro-p-indene-3,3'- 哚]-6-yl}oxy)tetrahydropyrrole_ι_remediate third-butan. 6-[(3R)-tetrahydropyrrole-3-yloxy]-1,-[(2 magic- Tetrahydrofuran-2-ylmethyl]spiro[[benzofuran-3,3'-indole]-2'(1Ή)-one hydrochloride; 3-[(2'-keto-1'-{[ 5-(trifluoromethyl) dimethylbutanyl]methyl}1,,2,dihydro sulphur benzopyrene-3,3'-theta ]]-6-yl)oxy]tetrahydro ρ Bilo_ι_slow acid third vinegar. (3S)-6-decyloxy-5-methyl-indole-[(4-methylhexahydropyranyl)methyl]-spirobenzopyrene -3-3,3'-啕嗓]-2'(1Ή)-keto hydrochloride; (3R)-6-methoxymethyl]4(4·decylhexahydropyridinium+yl)methyl Spirulina-3,3'-throindole-2((1Ή)-one hydrochloride; hydrogen snail [1- benzofuran-3,3,-hydrospiro[1- benzofuran-3 ,3,- 6-hydroxy-l'-(4-methoxybenzyl)_2'-keto_ι,,2,_di W哚]-5-indolecarbonitrile; 6-fluoromethoxybenzyl Base), keto, ι', 2, _ succinyl]-5-carbonitrile; Γ-(diphenyl phthalonitrile; yl)-2&lt;-keto-oxime, 2,-dihydrospiro 1-benzopyran-3,3'-哚]-6-曱143924-sp-20091127-6 -67- 201020257 Γ-(diphenylmethyl)_5,6-difluorospiro[1- benzofuran-3,3'-啕哚]-2' (1Ή)-ketone; 1Ηdiphenylmethyl)-6-(2-methoxyethoxy)spiro[1-benzofuran-3,3'-啕哚]-2Χ1Ή)-one; 5- ( Benzyloxy)-indole-(diphenylmethyl)spiro[1-benzofuran_3,3,_吲哚]-2,(ΓΗ)-one; Γ-(diphenylmethyl)-5-carboxyl Snail [1-benzofuran_3,3'_吲哚]-2'(1Ή)-one; Γ-(diphenylfluorenyl)-5-(2-methoxyethoxy) snail [1- Benzofuran_3,3,_峋哚]-2'(1Ή)-one; (diphenylmethyl)-2,3-dihydrospiro[吱,[2,3-f][l,4 Benzodioxanthene-7,3'-啕哚]-2'(1Ή)-one; Γ-(diphenylmethyl)spiro[furo[3,2^2^3]benzoindole Diazole _8,3,_蚓哚]-αΐΉ)-one; 6-chloro-1′-(diphenylmethyl)-2,3-dihydrospiro[吱,[3,2-f] [l,4]benzodioxanthene-9,3'-吲哚]-2,(1Ή)-one; 1'-(diphenylfluorenyl)-9-fluoro-2,3-di Hydrogen-spiro [aceto[2,3-g][l,4]benzodioxanthene-8,3'-吲哚]-2'(1Ή)-one; quinodiphenyl) -7,8-dihydro-6Η-spiro[furo[2,3-g]nonene_3,3,-啕哚]-2'(1H)-ketone; 1'-(diphenylfluorenyl) snail [pyrano[2,3-g]quinoxaline-8,3,,哚]-2,(1Ή)- Ketone; 6-methoxy-2'-keto-l',2,-dihydrospirobenzofuran_3,3,-啕哚]-5-carbonitrile; 6-fluoro-2'- _基-l',2'-dihydrospiro[ι_benzofuran_3,'3,-啕哚]-5-indoleonitrile; 2-yl-1,2-yl-II snail[1-benzene And biting -3,3'-Μ丨嗓]-6-曱 gambling; 2,3-dihydrospiro[furo[3,2_叩,4]benzodioxanthene_93,_ρ5丨哚]-2·(1Ή)-ketone; 5,6-difluorospiro[1-benzopyrano_3,3·_峋哚]·2,(ι,η)-one; 143924-sp-20091127 -6 -68- 201020257 6-(2-decyloxyethoxy)spiro[丨-benzofuran_3,3,_p?丨哚]_2,(1Ή)one; 5-(2-methoxyl) Ethoxy)spiro[丨_benzofuran_3,3,_ 哚 哚]_2, (111)-ketone; 2,3-dihydrospiro[furo[2,3 f][1,4]benzene And dioxin-terpene _7,3,峋哚]-2'(ΓΗ)-one; sulphate[2,3-g] oxaline _8,3'-吲哚]-2· (1Ή)-ketone; 2'-mercapto-l'-(P-pyridyl-2-ylmethyl)-Γ,2,dihydrospiro[丨benzofuran_3,3,啕哚]-6-甲Nitrile; 1 -(2'3-dihydro-1,4-benzodioxanthene_6 _ylmethyl)_2,·keto-indole, 2,_dihydroindole snail [1_benzopyran-3,3'-〇5丨嗓]-6-carbonitrile; P-Ο比 bite- 2-based fluorenyl) snail [Ρ 喃 并 笨 笨 噚 噚 _ _ _ _ _ _ _ _ _ _ _ 1 1 1 1 1 1 1 呋 呋 呋 呋 呋 呋 呋 呋 呋 呋 呋Benzobenzoxazole _8,3,_ρ丨哚丨哚]-2'(1Ή)-one; 4-[(5,6-difluoro-2'-oxaspiro[1_benzofuran_3, 3,_mercapto)methyl]hexahydropyridin-1-butylic acid tert-butyl ester; ❹ 6-(2-methoxyethoxy)-fluorene-(pyridin-2-ylindenyl) Snail [1-benzofuran_3,3,_吲哚]-2'(1Ή)-one; 5-(2-methoxyethoxy)_1,-(pyridin-2-ylmethyl) snail [1·benzofuran_3,3,_吲哚]-2\1Ή)-one; 1 acridine-2-ylmethyl)-2,3-dihydrospiro[吱,[2,3- f][l,4]benzodioxanthene-7,3'-吲哚]-2'(1Ή)-one; 1 _{[3-(dimethylmethyl)ρ ratio bite_2-曱]曱基}-2,3-dihydrospiro[ρ夫嚼[2,3_f][i,4] benzodioxanthene-7,3'-吲哚]-2·(1Ή) -ketone; methoxy-indole-(4-methoxybenzyl)_2|-keto-1,2'-dihydrospirobenzofuran 143924-sp.20091127-6 -69- 201020257 -3, 3'-吲哚]-5-carbonitrile; 6- Oxy-2,-keto-1,7-pyridyl-2-ylmethyl)4',2,-dihydrospirobenzofuran-3,3·-吲哚]-5-carbonitrile; 6 -fluoro-2-,-keto-oxime-(puppyridin-2-ylmethylΗ',2,-dihydrospirobenzofuran-3,3'-吲哚]-5-carbonitrile; 6 -Fluoro-2'-keto_1'_[(2 _ tetrahydrofuran 2 yl fluorenyl η,, 2, dihydrospirobenzofuran-3,3'-吲哚]-5-曱Nitrile; 6-fluoro-2-(-keto)-142-(trifluoromethyl celyl)-indole, 2,-dihydrospiro[indolobenzofuran-3,3'-indole]-5-indolecarbonitrile ; 6-fluoro I-keto-Γ·{[3_(trifluoromethylcyclopyridyl)methyl}1,,2,dihydrospiro[1-benzofuran_3,3·-吲哚]-5-carbonitrile; 1 (4 bromo + yl)-5,6-fluorospiro[1-benzo ρ 喃 _3,3,_吲嗓]•αρη) ketone; 5.6-difluoro- L'-(3-Mercaptobutyl) snail [μ笨和furan_3,3,_吲哚]_2,(ιή),; 5.6-difluoro-indole-(pyridine-2-ylindenyl) snail [1_benzofuran_3,3,吲哚]_2,(ΓΗ) ketone; 5,6-difluoro-indole-(tetrahydro-2Η-piperidin-4-ylmethyl) snail fl_benzo Furan _3,3,吲哚]-2'(1Ή)-one; 1 _{[5-(hydroxy) acridine-2-yl] fluorenyl} sulphate [e, benzene And two -8,3'-吲哚]-2'(1Ή)-one; 6-(2-decyloxyethoxy)-indole-[2-(2-decyloxyethoxy)ethyl] snail Stupid and sulphur-3,3'-吲哚]-2'(1Ή)-one; 5-(2-decyloxyethoxy)-indole-[2-(2-decyloxyethoxy) Ethyl] snail and snoring -3,3·-啕哚]-2Χ1Ή)-ketone; Γ-{[3-(tri-Imethyl)ρ-pyridin-2-yl]methyl} snail And [3,2_e][21,3]benzo 143924.sp-20091127-6 -70- 201020257 oxadiazole-8,3'-吲哚]-2ΧΓΗ)-one; 1'-{[3-( Trifluoromethyl oxaridin-2-yl]methyl}-2,3-dihydrospiro [bito-and-[3,2_叩,4] benzodioxanthene-9,3·- 哚]-2'(1Ή)-ketone; 5.6-monofluoro-1'-(hexahydro-p-indol-4-ylmethyl) snail [1-benzo-baked _3,3'_ 4丨哚]- 2\1Ή)-ketohydrochloride; 5.6-fluoro-l'-[(l-methylhexahydro-p-indol-4-yl)indolyl]spiro[1-benzopyrene 0 south_3,3 '_叫丨哚]-2'(1Ή)-ketohydrochloride; Ν',6-dihydroxy-indole-(4-methoxybenzyl)-2'-keto-oxime, 2'-di Hydrogen snail [1_benzopyrano -3,3:4 bud]-5- quinone imine amide; 6-hydroxy-2·-keto-l'-[(2R)-tetrahydrofuran-2 -ylindolyl]_1,,2,-dihydrospiro[μbenzofuran-3吲哚]-5-carbonitrile; 6-hydroxy-2'-keto(tri-Imethyl)hanyl]-ΐ',2'-dihydrospiro[1_benzofuran-3,3·-thirsty] -5-carbonitrile; l'-[(5-chloro-2-4phenyl)indolyl]-5-(6-decyloxyindole-3-yl)spiroquinone-p-pyran--3 , 3. 5 丨哚]-2·(1Ή)-ketone; • 5,6-difluoro-l'-{4-[(3R)-tetrahydroρ than indol-3-ylamino)] Spiro[1_benzohepta-3,3'-吲哚]-2'(1Ή)-keto hydrochloride; 9-fluoro-2,3-dihydro-spirophtho[2, 3-g][l,4]benzodioxanthene_8,3,-4丨哚]-Τ(ΓΗ)-one; 7,8-dihydro-6Η-spiro[吱喃[2 ,3-g]decene-3,3'-啕哚]-2, (qiet-ketone; 6-chloro-2,3-dihydrospiro[c-buto[3,2-f][l, 4] benzodioxanthene _9,3,-吲哚]-2'(1Ή)-one; snail [3,2&lt;][2,1,3] stupid oxadiazole _8,3',哚]-2,(1)-ketone; 6-chloro-indenyl-pyridin-2-ylmethyl)-2,3-diindole[吱,[3, 2-f][l,4]benzodiazepine 143924-sp-20091127-6 -71 · 201020257 Oxygen decene-9,3 W pollo]-2'(1Ή)-one; Γ-(acridine- 2-ylmethyl)-2,3-dihydrospiro[吱,[3,2-f][l,4]benzodioxanthene-9,3'-啕哚]-2' ( 1 beer - 9-Fluoro-indenyl-(acridin-2-ylmethyl)-2,3-dihydro-spiro[Miso-[2,3-g][l,4]benzodioxan -8,3'-吲嗓]-2'(1Ή)-one; 9-fluoro-indole-{[3-(trifluoromethyl)acridin-2-yl]methyl}-2,3- Dihydrospiro[吱,并,P,3-g][l,4]benzodioxanthene _8,3·-沔1嗓]-2,(1Ή)-one; 9-fluoro-anthracene -[(5-hydroxypyridin-2-yl)indolyl]-2,3-dihydrospiro[furo[2,3-g][l,4]benzodioxolene weib]- 2'(1Ή)-one; 6-(5-methyl-1,2,4-oxadiazol-3-yl)-indole-(pyridin-2-ylmethyl)spiro[1-benzofuran- 3,3'-吲哚]ΚΓΗ)-ketone; or 6-alkyl-indole-{[3-(trifluoromethyl)ρ-pyridinyl-2-yl;j-yl}_2,3-dihydrospiro Bufmano[3,2-f][l,4]benzodioxene _9,3,_啕哚. 17. - Compound of formula (V): Wherein: R9 is hydrogen R is wind, dibenzyl, [5-(trifluoromethyl)pyran-2-yl]methyl, (2r)_tetrahydrofuran-2-ylmethyl, pyridine_2_yl Base, (Shen)", dioxerean, _2_ylmethyl or (2S)-1,4-dioxoindole-2-ylmethyl; its stereoisomers, palmomers, mutual An isomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 143924-sp-20091127-6 -72· 201020257 18. The compound of claim 17, which is selected from the group consisting of: Γ-(diphenylmethyl)-3,4-dihydro-2H-spiro[furo[2, 3-h][l,5]benzodiazepine heptarene-9,3'-W 哚]-2·(1Ή)-one; 3,4-dihydro-2Η-spiro [furan P, 3-h][l,5]benzodiazepine heptarene-9,3·-吲哚]-2'(1Ή)-one; Γ-{[5-(trifluoromethyl)furan-2 -yl]methyl}-3,4-dihydro-2-indole-spiro[吱,[2,3-h][l,5]benzodioxineseptene oxime-0-pyridin-2-yl Methyl)-3,4-dihydro-2H-spiro [bito-and-[2,3-h][l,5]benzodioxole-7-nitridin-9,3·- 哚 哚]-αΐΉ )-ketone; 1'-[(2 ft)-tetrahydrofuran-2-ylindenyl]-3,4-dihydro-2-indole-spiro [bito-and-[2,3-h][l,5] benzo Dioxo-heptene-9,3'-吲哚]-2'(1Ή)-one; r-[(2R)-l,4-dioxaindole-2-ylmethyl]-3/l · Diterpene-2Η-spiro[furo[2,3-h][l,5]benzodioxaqiheptene-9,3,-吲哚]-2,(1Ή)-one; or r -[(2S)-l,4-dioxolyl-2-ylmethyl]-3,4-dihydro-2-indole-spiro[furo[2,3-h][l,5]benzoic Oxygen nitrogen heptasaccharide-9,3'-嗍哚]-2·(1Ή)-ketone. 19. A compound of formula (VI): Wherein: Ζ is -Ο- or -Ν〇Η)-; R10 is hydrogen, 3-methylbutyl, 4-methoxybenzyl, 2-(2-methoxyethoxy)ethyl, 4 -isoxazol-5-ylbenzyl, 2-(trifluoromethyl)benzyl, [3-(trifluoromethyl]pyridin-2-yl]indolyl, [4-( via carbonyl) Zin-2-yl]methyl, [4-(Ν,Ν- 143924-sp-20091127-6 •73· 201020257 dimethylaminocarbonyl), oxazol-2-yl]methyl, (4-cyano) Methylcarbonyl)benzyl, [5-(di-indenyl)oxy-2-yl]indenyl, (2R)-tetrahydro-p-flavor-2_ylindenyl, (3-fractor p-pyridyl) -2-yl)methyl, [4-(methoxycarbonyl)p-oxazol-2-yl]methyl, 4·(3_amino·1Η-external b ° sit-5-yl) nodal group, ρ ratio Biting 2_yl thiol, biting _3_yl fluorenyl or pyridin-2-yl fluorenyl; and R1Qa is hydrogen, fluorenyl or -NH2; for its stereoisomers, palmar isomers, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 20. The compound of claim 19, wherein z is _〇_ or _N(H)_, and R1 〇a is 氲❿ or methyl. 21. The compound of claim 20, which is selected from the group consisting of: 1-[2-(difluoromethyl) Base;]_1H^ Fudan[3,2_ 吲 吲 _5,3,_吲哚]_ 2Χ1Ή)-ketone; Γ-(pyridin-2-ylmethyl)-lH-spiro And [3,2_f]carbazole _5,3,_ 哚 哚] 2,(1Ή)_ class; 1 -((3-(difluoromethyl)pyridinium-2-yl)methyl hydrazine, 6 Dihydrospiro [bito-[3,2 phantomazole-5,3'-dihydroanthracene]-2'-one; © 1'-(4-methoxybenzyl)-3-methyl snail (&gt; Furan[3,2_£][1,2]benzisoxazole_5,3,_吲哚]-2 丫1Ή)-one; 3methylspiro[吱,[3, 2-f][l,2]benzoindole p-嗤5,3'-ρ5丨嗓]_2'(1Ή)-one; 3-methyl-1,-{[5-(trifluoromethyl) ) 吱 · 2 2 ] ] 甲基 甲基 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 (pyridin-2-ylmethyl)spiro[吱,[3,2_q[1,2] benzisoxazole-5,3W 丨哚]-2·(1Ή)-one; 143924-SP-2009H27- 6 •74· 201020257 3-Methyl-indole-(pyridin-3-ylmethyl)spiro[吱,[3,2-f][i,2]benzisoxazole-5,3-^1 ^ ]-2'(1Ή)-ί^ ; 3-Methyl-l'-[(2R)-rahydrofuran-2-ylmethyl]spiro[吱,[3,2_叩,2]benzene And the same number of saliva-5,3·-θ 丨嗓]-2'(1Ή)-ketone; l'-(4-isoxazol-5-ylindenyl -3-indolyl snail [furan ρ,2_η[12] benzisoxazole-5,3·- 哚 哚]-2'(1Ή)-one; 3-methyl-1·-[2-( Trifluoromethyl) argyryl] snail [味喃[3 2_叩,2] benzisoxazole-5,3Μ卜朵]-2'(1Ή&gt;ketone; ❿ 3_methyl-"([ ΗTrifluoromethyl oxaridin-2-yl] fluorenyl} snail [吱 benzo benzopyrene-5,3·-θ丨嗓]·2·(1Ή)-ketone; [-[--(2) Methoxyethoxy oxime ethyl sand methyl snail 吱 即 即 叩 苯 苯 benzoisoxazole-5,3·- 哚 哚]-2' (1 Ή)-ketone; 3-methyl-oxime -(3-methylbutyl)spiro[吱,[3,2-f][l,2]benzisoxazole-5,3,-throindole]-2'(1Ή)-one; 3 -Methyl-indole-(pyroxy-2-ylindenyl) snail [吱 并[3,2 韵ι,2] benzisoxazole_5,3,-mouth mouth]-2,( 1Ή)-嗣; Φ 14(3-Fluoro-based ρ-but-2-yl)methyl]-3-methylspiro (&gt; Furan[3,2-:η[1,2] benzimiphth Oxazol-5,3'-吲哚]-2'(1 ugly)-keto; 2-[(3-methyl-2'-oxaspiro[furo[3,2-hunt 1,2] benzo Isoxazole-5,3,-4 哚]-1·(2Ή)-yl)methyl]-1,3′′ oxazole carboxylic acid oxime ester; 2-[(3-methyl-2: oxane) [bite and [3,2-f][l,2] benzopyrene 嗤-5,3Ί嗓]_ Γ(2 Ή)-yl)methyl hydrazine, 3-oxazole-4-carboxylic acid; hydrazine, hydrazine-dimethyl-2-[(3-methyl-2.-oxaspiro[吱,[3,2- ))[1,2]benzoxazole-5,3'-p5l **1](2Ή)-yl)indolyl]-1,3-»» ; 143924-SP-20091127-6 -75- 201020257 3-{4-[(3-Methyl-2'-oxaspiro[furo[3,2-f][l,2] benzisoxazole_ 5,3'-thraquinone]-1'(2Ή)-yl)methyl]phenyl}-3-ketopropanonitrile; or 1·-[4-(3-amino-1Η-pyrazole-5 -yl)mercapto]-3-methylspiro[吱,[3,2-f][l,2] benzisoxazole-5,3L吲哚]-2'(1Ή)-one hydrochloride salt. 22. The compound of claim 19, wherein the rule 1 () 3 is - see 12. 23. The compound of claim 22, which is selected from the group consisting of: 3-amino-l'-(4-decyloxybenzyl) spiro[oleno[3,2-f][l,2]benzo Isoxazol-5,3·-吲哚]-2'(1Ή)-one; 3-amino-indole-(pyridin-2-ylmethyl) snail [bito-[3,2-f][ 1,2] benzoisoxazole © -5,3'-吲哚]-2·(1Ή)-one; 3-amino-1'-[(211)-tetrahydrofuran-2-ylmethyl] snail [Nitrate [3,2-f][i,2] benzisoxazole-5,3'-吲哚]-2·(1Ή)-one; or 3-amino-1·-[2 -(Trifluoromethyl)octyl]spiro[吱,[3,2_耶,2]benzoiso-oxazole-5,3'-吲嗓]-2'(1Ή)-one. 24. —Formula (νπ) Compound: Ν V-ch3 (VII) . \r11 . &gt; where: Y is -Ο- or -S-; R is hydrogen, diphenylmethyl, 3-methylbutyl, tetrahydro-2-indole_pyran-4曱 曱 、, (2R)-tetrahydrofuran-2-yl fluorenyl, pyridin-2-ylmethyl or (5-hydroxy-indenyl-1Η-imidazol-2-yl)methyl; Palmomers, tautomers or mixtures thereof, 143924-sp-20091127-6 •76- 201020257 or a pharmaceutically acceptable salt, solvate or prodrug thereof. 25. The compound of claim 24, which is selected from the group consisting of: 2-mercaptospiro[吱,[2,3-f][l,3]benzopyrazolium]-2, (1Ή)-one; Γ-(diphenylfluorenyl)_2-fluorenyl snail [ρofrano[2,3-f][l,3]benzoxazole-7,3,- 哚 哚]-2'(1Ή)- Ketone; 2-mercaptospiro[吱,[2,3-f][l,3]benzoxazole-7,3'-吲哚]-2,(1Ή)-one; 2-indolyl- Γ-(3-methylbutyl) snail [cough benzopyrimazole_7,3,_吲哚]-2'(ΓΗ)-one; ® 2_methyl s(5)hydro-2Η-»派喃-4-ylmethyl) snail [吱,[2,3-f][l,3]benzoxazole-7,3'-啕哚]-2,(1Ή)-one; 2-A -R-[(2R)-E9hydrofuran-2-ylmethyl]spiro[吱,[2,3-f][l,3]benzoxazole-7,3·-,?丨哚-2'(1Ή)-ketone; 2-indolyl-indole-(acridin-2-ylindenyl) snail [ρ 喃 并 阳 (3) benzopyrazole _7,3·_ 吲哚]- 2'(1Ή)-ketone; or L'-[(5-Chloro-1-indolyl-1Η-imidazol-2-yl)indolyl]_2·indolyl snail [吱,[2,3-f][l,3]benzopyrimidine Azole-7,3'-吲哚]-2,(1Ή)-®Ι. W is a direct bond or -CH2-; and R2 is a wind, a thiol group or a (2R)-tetrahydrofuran-2-ylmethyl group; its stereoisomers, palmomerisomers, tautomers A construct or a mixture thereof; 143924-sp-20091127-6 • 77- 201020257 or a pharmaceutically acceptable salt, solvate or prodrug thereof. 27. The compound of claim 26, wherein w is a direct bond. 28. The compound of claim 27, which is selected from the group consisting of: Γ-(diphenylhydrazinyl)-1-methylspiro[吱,[3,2 幻旧]benzoxazole_7 3,_吲哚]-2,2·(1Η,1Ή)-dione; 1-methylspib-butan[3,2-f][l,3]benzo-oxazole_7,3,-W 哚] -2,2,(1Η,1Ή)-dione; or 1-mercapto-r-[(2R)-rahydrofuran-2-ylindenyl] snail [吱,[3,2〇[1, 3] Benzosazole-7,3'-吲哚]-2,2'(111,1 ugly)-dione. 0 29. The compound of claim 26, wherein W is -CH2-. 30. The compound of claim 29, which is selected from the group consisting of: Γ-(diphenylfluorenyl H-indenyl-1H-spiro[吱,[3,2-g][l,4]benzoindole- 8,3·- 哚 哚]-2,2'(1Ή,3Η)-dione; 1-methyl-1Η-spiro[&gt;Furan[3,2-g][l,4]benzo噚耕-8,3W丨哚]-2,2^1Ή,3Η)-di-class; or 1-methyl-r-[(2R)-rahydrofuran-2-ylmethylHH-spiro[吱And [3,2-g][l,4]benzoindole-8,3,-(tetra)indole-2,2,(1Ή,3Η)-dione. — 31. — Compound of formula (IX): ch3 N~ Wherein: u is a direct bond or -ch2-; and 143924-sp-20091127-6 201020257 Rl3 is hydrogen, diphenylfluorenyl, [5-(trifluoromethyl)pyran-2-yl]fluorenyl or ( 2R)-ra hydrofuran-2-ylmethyl; a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof . 32. The compound of claim 31, wherein u is a direct bond. 33. The compound of claim 32, which is selected from the group consisting of: 1 L (diphenylmethyl)-3-methylspiro[吱,[2,3-phan [1,3]benzoxazole-7,3 ,-啕嗓]-2,2,(1·η,3Η)-dione; ® mercaptospiro[Octa[2,3-f][l,3]benzoxazole-7,3, -吲哚]-2,2,(1Ή,3Η)-dione; 3_methyl 4,7-5-(trifluoromethyl)indol-2-yl]methyl}spiro[吱喃和[2 , 3-f][l,3] benzoxazole _7,3'-吲哚]-2,2'(1 brother 311)-dione; or 3-methyl-1'-((( _tetrahydrofuran_2_yl)indenyl)_211_spiro[benzofuro[6,5_d] p-indole-7,3'-dihydroanthracene-2,2,(3H,6H)-dione 34. The compound of claim 31, wherein u is _Ch2-. 35. The compound of claim 34, which is selected from the group consisting of: 9 4-methyl-4,7-dihydrospiro[benzofuran[ 5,6-b][l,4]噚耕-8,3,-dihydroanthracene-2,3(2H)-dione; or 4-mercapto-r-[(2R)-iz9 Hydrofuran-2-ylmethyl]-2H-spiro [bito-and-[2,3-g][l,4]benzoindole-8,3·-峋哚]-2,,3 (1Ή, 4Η)-dione. 36. —Formula (Χ) compound: (X) 143924-sp-2009l 127-6 •79· 201020257 is a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or pharmaceutically acceptable salt thereof Body medicine. 37. The compound of claim 36 which is broad (6) phantom hydrogenfuran-2-ylmethyl] snail [benzo[l,2-b:5,4-b^furan-3,3,-啕哚] Ud'HAH)-dione. 38. - Compound of formula (XI): Where: V is -0-, _n(ch3)- or -ch2_, and Y is _n(CH3)- or -CH2-; or V is -N(CH3)- or -CH2-, and 丫 is _〇 _, _n(Ch3)_ or -Ch2_; and R is hydrogen, [5-(difluoroindolyl)indol-2-yl]methyl, p is more than _2 yl fluorenyl, p_ (trifluoromethyl) Acridine-2-yl]methyl or (2R)-tetrahydrofuran-2-ylmethyl; a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable Accepted salts, solvates or prodrugs. 39. The compound of claim 38, wherein both ¥ and ¥ are _cH2_. 4. A compound according to claim 39, which is selected from the group consisting of: 1 Benzylmethyl&gt;5|,6',7',8|-tetrahydrospiro[3,3,_茶和[2 3 b]furan]_2(10)_ ketone; 5',6''7',8'_tetrahydrospiro[10 _3,3,_荇[2,3-7]furan]_2(10) ketone; or 1-[( 2 to do tetrahydrofuran-2-ylmethyl]-5,,6,,7,,8,_tetrahydrospiro [old 哚3,3,_荇[2,3-b]furan]-2 (1H A ketone. The compound of claim 38, wherein v is _〇_, and γ is _n(ch3)_. 42. The compound of claim 41, which is selected from the group consisting of: 143924-sp-20091127-6 •80· 201020257 1-mercapto_1'-{[5-(trifluoromethyl) sulfhydryl] fluorenyl}_2,3_dihydro____[[2,2-g ][l,4]benzoindole _8,3,_巧哚]_2, (1Ή)-keto hydrochloride; or 1-methyl-l'-[(2R)-W-hydrofuranyl fluorenyl ]_2,3_Dihydroanthracene snail [唉,[3,2-g][l,4]benzobenzine _8,3'-吲哚]-2,(1Ή)-ketone hydrochloride 43. The compound of claim 38, wherein V is -N(CH3)-, and Y is 44. The compound of claim 43 which is 4 fluorenyl _r_[(2R)_tetrahydrofuran Methyl]-3'4-dihydro-2H-spiro [biting and arranging [2,3_ g][1,4] Benzene, 8,3,吲哚]-2·(1Ή)-ketone. 'β 45. The compound of claim 38, wherein ¥ is even_, and _〇_ 46. The compound of claim 45, which is selected from the group consisting of: Γ-(pyridin-2-ylindenyl), 7,8-dihydro-6, snail-[furan[2 3 g] decene%,啕哚]-2,(1Ή)-ketone; or, 1][3-(difluoroindolyl)ρ than bite_2·yl]methyl}-7,8-dihydro-6Η-spiro Methyl [2,3-g]nonene_3,3,-吲哚]-2,(1Ή)-_. 47. Compound of formula (XII): R1 a is hydrogen or (acridin-2-yl)methyl; is a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate thereof or Prodrugs. 48. The compound of claim 47, which is selected from the group consisting of: 143924-sp-20091127-6-81-201020257 6-mercapto-oxime-0-to-but-2-ylindenyl)-2,3-dihydrogen Spirulina [1,4-dioxolanoxa[2,3-f] 啕哚-8,3'-θ丨哚]-2',7(ΓΗ,6Η)-dione; or 6-methyl -2,3-dihydrospiro[1,4-dioxoland rare [2,3_f] η丨ρ朵_8,3'_β丨哚]-2',7(1Ή,6Η)-two ketone. 49. A compound of formula (XIII): Wherein: Ε is -0- or -CH2-; J is -〇- or -CH2-; u is a direct bond or -CH2-; and Rlb is hydrogen, [3-(trifluoromethyl) a thiol, diphenylmethyl or [5-(trifluoromethyl)furan-2-yl]methyl; a stereoisomer, a palmomer, a tautomer or a mixture thereof; A pharmaceutically acceptable salt, solvate or prodrug. 50. A compound according to claim 49, which is selected from the group consisting of: 1_(monomethyl)-2,3,6,7-tetrahydrospiro[吱Taste [3,2-苢] olefin _5,3,-1»丨嗓丨嗓]-2'(1Ή)-ketone; Γ-{[3-(trifluoromethylcyclopyridine_2_yl) Methyl}-7,8-dihydrospiro[1,4-dioxolynene[2,3-g][l,3]benzodioxolene-4,3,-吲哚] -2,(1Ή)-one; 2,3,6,7·tetrahydrospiro[吱,[3,2-gK-ene-5,3,-啕哚]-2,(1,Η)-one ; or 1 -{[5-(二敦methyl)吱锋_2_yl]methyl}-2,3,6,7-tetrahydrospiro [biting β南和p,2_g] 143924-sp-20091127 -6 -82- 201020257 and the like, wherein the pharmaceutical composition comprises a pharmaceutically acceptable excipient, the compound of any one of items 1 to 50, which is stereoscopically different Structure, structure, An isomer or a mixture thereof; or a pharmaceutically acceptable solvate or prodrug thereof. 52. A method of treating, preventing or ameliorating a disease or condition in a mammal, the disease or condition being selected from the group consisting of Group: pain, depression, cardiovascular disease, respiratory disease, and psychiatric disease, and combinations thereof, wherein the method comprises administering a therapeutically effective amount to a mammal in need thereof, as claimed in any one of 50 a compound, which is a stereoisomer, a palmo isomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, a solvent person or a prodrug. Port 53. The method of claim 52, The disease or symptom is selected from the group consisting of neuropathic pain, inflammatory pain, (d) (iv), cancer pain, chemotherapy pain, traumatic pain, surgical pain, post-operative pain, production pain, pain relief, Nervous bladder, ulcerative colitis, chronic pain, persistent pain, pain in the distal media, toothache, pain in the media, chronic headache, migraine, sinus The method of claim 52, wherein the disease or symptom is selected from the group consisting of: pain and clothing associated with HTV. Neuropathy caused by treatment, tri- and neuralgia, post-operative neuropathic pain, normal pain, heat sensitivity, local sarcoidosis, irritant pure (4), Crohn's disease, pain associated with multiple sclerosis, muscle Atrophic lateral sclerosis (ALS), diabetic patients 143924-sp-20091127-6 -83· 201020257 Neuropathy, peripheral neuropathy, arthritis, rheumatoid arthritis, osteoarthritis, atherosclerosis, paroxysmal muscle tension Insufficient, muscle weakness syndrome': tonic, malignant hyperthermia, cystic fibrosis, pseudo aldosteronism, rhabdomyolysis, hypothyroidism, bipolar depression, anxiety, schizophrenia, nanochannel toxin-related diseases, familial acromegaly Pain, primary acral red pain, familial rectal pain, cancer, epilepsy, partial and general tension, restless foot stagnation, irregular rhythm, fiber Myalgia, neuroprotection in the state of blood stasis caused by wind or nerve damage, rapid rhythm, atrial fibrillation, and ventricular fibrillation. 55. A method of treating pain in a squirting animal by inhibiting ion flux through the electro-devil-dependent nanochannel in the Wei animal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount A compound according to any one of the preceding claims, which is a stereoisomer, a palmomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable prodrug thereof. a method of reducing the flux of ions through a voltammetric channel in a mammalian cell, wherein the method comprises contacting the cell with a compound of the formula Is a stereoisomer, a pair of tautomers or mixtures thereof; or a pharmaceutically acceptable salt thereof: a composition or prodrug. 57'-A method for treating hypercholesterolemia in a mammal. A mammal in need thereof is administered a therapeutically effective amount of a compound as claimed in any one of the claims - as a stereoisomer tautomer thereof or a mixture; or a pharmaceutically acceptable salt thereof, ΓΓ 143924-sp-2〇〇9i 127-6 -84 - 201020257 or a prodrug. 58. A method of treating benign prostatic hyperplasia in a mammal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound according to any one of claims 1 to 49, An isomer, a palmo isomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 59. A method of treating a pain in a mammal, wherein the method comprises administering to the mammal in need thereof a therapeutically effective amount of a compound such as a requesting worker to any one of An isomer, a palmo isomer, a tautomer or a mixture thereof; or a pharmaceutically acceptable salt thereof, a solvating prodrug. 60. A method of treating cancer in a mammal, wherein the method comprises administering to a mammal having a therapeutically effective amount of a compound according to any one of claims (1), a stereoisomer thereof, An isomer, tautomer, or a mixture thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof. 143924-sp-20091127-6 -85· 201020257 IV. Designated representative map: (1) The representative representative of the case is: (none) (2) The symbolic symbol of the representative figure is simple: 5. If there is a chemical formula in this case, please Reveal the chemical formula that best shows the characteristics of the invention: 143924-sp-20091127-1 -2-